Choosing and changing opioids / opiates

Codeine

• Available as codeine phosphate tablets 15mg, 30mg and 60mg and as liquid preparations 15mg/5ml and 25mg/5ml.
• Also available in combination with paracetamol 8mg/500mg, 15mg/500mg, 30mg/500mg.
• Codeine must be metabolised to morphine to achieve most of its analgesic effect.
  • 5 to 10% of people lack the liver enzyme which enables this to happen (CYP2D6) and therefore pain relief will not be achieved but adverse side effects will still occur.
  • In contrast, ultra-rapid metabolisers produce more morphine and are more prone to toxicity.
• Several active metabolites are renally excreted.
• Avoid in stage 4 and 5 Chronic Kidney Disease.

• Maximum oral dose: 240mg/24 hours.

Dihydrocodeine

• Similar to codeine in structure and analgesic effect.
• Available as 30mg tablets
• Dihydrocodeine is metabolised by the liver enzyme CYP2D6 to an active metabolite.
• No evidence to suggest that analgesic effect is affected by an individual’s ability to metabolise dihydrocodeine.
• Active metabolites are renally excreted.
• Avoid in stage 4 and 5 Chronic Kidney Disease.
• Maximum oral dose: 240mg/24 hours.

Tramadol

• Oral and injectable dose forms available.
• Chemically unrelated to morphine. Opioid and non-opioid properties.
• Renally excreted.
• Use with caution in stage 4 and 5 Chronic Kidney Disease and severe liver failure. Consider increasing the dosage interval of the immediate release preparation to 12 hourly and to avoid the modified release preparation.
• Tramadol requires the liver enzyme CYP2D6 to help with its metabolism and can therefore be poorly tolerated by some individuals.
• Contra-indicated in individuals taking Monoamine Oxidase Inhibitors (MAOIs) or in those with epilepsy.
• Avoid or use with caution in individuals taking Selective Serotonin Reuptake Inhibitors (SSRIs) or Tricyclic Antidepressants (TCAs) due to risk of serotonin syndrome and of lowered seizure threshold.
• Maximum oral dose: 400mg/24 hours

Buprenorphine patches

• Available as a 7-day patch (for example Butec®). At low doses (5micrograms to 20micrograms/hr) is used to treat moderate pain.
• Buprenorphine patches are contra-indicated in patients with acute (short-term) pain and in those who need rapid dose titration for severe uncontrolled pain.
• Undergoes hepatic metabolism to norbuprenorphine which has little clinical activity and does not cross the blood-brain barrier.
• Unchanged buprenorphine is excreted through the biliary system.
• Buprenorphine does not accumulate in renal impairment and therefore may be a good Step 2 Opioid in stage 4 and 5 Chronic Kidney Disease.

Refer to buprenorphine information sheet.

Note: A 3-day patch (35microgram, 52.5microgram and 70microgram/hr) and a 4-day patch (35microgram, 52.5microgram and 70microgram/hr) are available. At higher doses (greater than 20microgram/hr), buprenorphine is used to treat moderate to severe pain. 

Morphine

(refer to morphine information sheet)

• Immediate and modified release oral preparations (ensure correct preparation is prescribed); subcutaneous (SC) injection and in syringe pump for continuous subcutaneous infusion (CSCI).
• Renally excreted, active metabolites – titrate morphine slowly and monitor carefully in stage 1 to 3 Chronic Kidney Disease.
• Use alternative opioids in stage 4 and 5 Chronic Kidney Disease and patients undergoing dialysis to avoid toxicity. Refer to End stage renal disease guideline.
• Consider low doses and slow titration in liver impairment.

Diamorphine

• Highly soluble opioid used for SC injection and in a syringe pump (CSCI).
• Use for high-dose SC breakthrough injections (above morphine SC bolus injections of 60mg [2ml]). Powder preparation is soluble in a small volume of water for injections.
• As with morphine, cautious use in renal and liver impairment. Avoid in stage 4 and 5 Chronic Kidney Disease.

Oxycodone

(refer to oxycodone information sheet)

• For moderate to severe pain if morphine/diamorphine are not tolerated.
• Immediate and modified release oral preparations (ensure correct preparation is prescribed); SC injection; syringe pump (CSCI).
• Lower concentration preparation limits dose for SC injection to 20mg (2ml). (In some NHS boards, a 50mg/ml injection is available – check local guidance.)
• Avoid in moderate to severe liver impairment, where clearance is much reduced.
• Mild to moderate renal impairment: reduced clearance so titrate slowly and monitor carefully.
• Avoid modified release preparations in stage 4 and 5 Chronic Kidney Disease. Immediate release preparations may be used with caution for breakthrough pain.
• Avoid use of Oxylan and Oxyact in people with soya and peanut allergy. 

Fentanyl

(refer to fentanyl patches information sheet and consider seeking specialist advice)

• Transdermal patch lasting 72 hours; use if oral and SC routes are unsuitable.
• Consider only if tolerant to opioids as this is a very potent opioid. A 12 microgram/hour fentanyl patch is equivalent to about 30mg to 60mg of oral morphine in 24 hours. Inappropriate use can cause fatal overdose.
• For stable pain if morphine not tolerated; dose cannot be changed quickly.
• No initial dose reduction in renal impairment but may accumulate over time as it is cleared through the kidneys. Consider changing every 96 hours if eGFR<30ml/min, pain is well controlled but the patient has shown signs of mild toxicity. Consider seeking specialist advice in this situation.
• Liver impairment; dose reduction may be needed in severe liver disease.
• Do not initiate in the last days of life when the oral route is no longer available (can take too long to reach steady state) – refer to fentanyl patches information sheet. If a patient is already on a fentanyl patch and in the last days of life, refer to fentanyl patches information sheet.

Alfentanil

(refer to alfentanil information sheet)

• Alfentanil is a potent opioid: 1mg of alfentanil is roughly equivalent to 30mg oral morphine.
• Short-acting, injectable opioid for SC injection and in a syringe pump (CSCI).
• In episodic/incident pain, it can be given sublingually (an unlicensed †spray is available) or subcutaneously.
• Dose does not need to be reduced in renal disease including stage 4 and 5 Chronic Kidney Disease.
• Clearance may be reduced in liver impairment; reduce dose and titrate.
• Drug of choice if eGFR<20ml/hr, although may be recommended  earlier by specialists and syringe pump required
• Useful if severe pain and toxicity.
• Please seek specialist advice when switching from a CSCI of alfentanil to an alternative opioid.

Fentanyl

sublingual/buccal/intranasal

• These are potent preparations. Before rapid acting fentanyl is used, patients must have been on a stable dose of a regular opioid for approximately 7 days equivalent to a minimum of 60mg oral morphine or 30mg of oral oxycodone in 24 hours or a
  25 micrograms/hour fentanyl patch.
• In episodic/incident pain, fentanyl can be given sublingually (Abstral®, Effentora®), buccal (Effentora®) or intranasally (PecFent® – check local guidance for preferred preparation and refer to Abstral®, Effentora® or PecFent® guidelines. These products are not interchangeable due to different absorption profiles.
• The effective dose of transmucosal fentanyl cannot be predicted from the background dose of opioid. Start at the lowest dose and titrate upwards to determine the effective dose.
• 100microgram fentanyl is approximately equivalent to 15mg of oral morphine.

Hydromorphone

(refer to hydromorphone information sheet)

• Potent opioid for specialist use only.
• Frail or elderly patients need smaller doses, less frequently with slower titration.
• Available in oral capsules and MR capsules and an unlicensed immediate release hydromorphone oral solutionⴕ. Hydromorphone can also be given by injection
• Liver impairment, reduced clearance. Start at a lower dose and closely monitor.
• Renal impairment, reduced excretion. Titrate slowly and closely monitor. Avoid in
  stage 4 and 5 Chronic Kidney Disease.
• At higher doses, consider medicines burden of breakthrough dose

Methadone

(refer to methadone information sheet)

• Potent opioid for specialist use only.
• Oral methadone is used by specialists for complex pain where other opioids have inadequate efficacy.
• Available in oral tablet and liquid form. Methadone can also be given by injection.
• Dosing is difficult due to the potentially long and unpredictable half-life.
• Partial renal and biliary excretion occurs therefore dose reduction may not be required in Chronic Kidney Disease.
• Half-life is prolonged in severe liver disease.
• Conversion from other opioids to methadone is complex and inpatient admission is advised.

Opioid/opiate conversion tables – switching between opioid medicines

Opioid toxicity

• Can be precipitated by several factors, including rapid dose escalation, renal impairment, sepsis, electrolyte abnormalities, drug interactions.
• Wide variation in the dose of opioid that can cause symptoms of toxicity.
• Prompt recognition and treatment are needed. Symptoms include:
• persistent sedation (exclude other causes)
• vivid dreams/hallucinations; shadows at the edge of visual field
• delirium
• muscle twitching/myoclonus/jerking
• abnormal skin sensitivity to touch (opioid induced hyperalgesia, OIH).
• If the pain is controlled, reduce the opioid dose by a third. Ensure the patient is well hydrated. Seek advice.
• If pain is uncontrolled, consider reducing opioid dose by a third. Consider adjuvant analgesics, alternative opioids or both. Seek advice.
• Naloxone (in small titrated doses) is only needed for life-threatening respiratory depression (refer to Naloxone guideline).

• Morphine injection is available in a maximum concentration of 30mg/ml.
• Oxycodone injection may only be available as 10mg/ml (50mg/ml injection may be available in some NHS boards).
• When giving SC opioid injections, the maximum volume is 2ml. If a patient needs a dose that is in an injection volume above 2ml – seek advice.

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