4.7.2 Opioid analgesics

For support when prescribing opioids please refer to formulary page Management of opioids and Opioids Aware: a resource for patients and healthcare professionals to support prescribing of opioid medicines for pain.

NPSA Rapid response July 2008: reducing dosing errors with opioid medicines:

When opioid medicines are prescribed, dispensed or administered, in anything other than acute emergencies, the healthcare practitioner concerned, or their clinical supervisor, should:

  • Confirm any recent opioid dose, formulation, frequency of administration and any other analgesic medicines prescribed for the patient, through discussion with the patient or their representative, the prescriber or through medication records (exercise care in accepting self-report from patients with dependence or suspected drug dependence)
  • Ensure where a dose increase is intended, that the calculated dose is safe for the patient

Specific dosage instructions should be written on the prescription, i.e. "X to be taken x hourly when required for pain" as well as a maximum daily dose, rather than simply "PRN". This ensures a maximum dose is stated and will prevent dose escalation without prescriber approval.

All slow release opioids should be prescribed by brand name.

Renal impairment alters the clearance of parent opioid compounds and also affects the accumulation of metabolites. This varies for individual opioids; an understanding of the pharmacokinetics of each drug is important to minimise the risk of toxicity. Refer to the BNF, individual Summary of Product Characteristics and specialist for further guidance.

The BNF recommends that the use of opioids in patients with hepatic impairment should be avoided or the dose reduced; opioids may precipitate coma in patients with hepatic impairment.

Weak Opioids

Compound preparations containing paracetamol and codeine can be found here

Codeine phosphate
  • Tablet 15mg, 30mg, 60mg (£0.88= 30mg x 28 tablets)
  • Oral solution 25mg in 5ml (£6.46 = 500ml)

Indications

Dose

  • Adult over 18 years, 30–60mg every 4 hours when necessary, to a maximum of 240mg daily

Notes

  1. Codeine is useful for the relief of mild to moderate pain but is too constipating for long-term use.

Strong Opioids

Diamorphine hydrochloride
  • Injection 5mg, 10mg, 30mg, 100mg, 500mg (£13.62 = 30mg x 5 ampoules)

Indications

Dose

  • Acute pain, by subcutaneous or intramuscular injection, 5mg repeated every 4 hours if necessary (up to 10mg for heavier well-muscled patients); by slow intravenous injection, quarter to half corresponding intramuscular dose
  • Chronic cancer pain, by subcutaneous or intramuscular injection
    • Adult not currently treated with a strong opioid analgesic, initially 2.5–5mg every 4 hours, adjusted according to response
    • Adult, by subcutaneous infusion, not currently treated with a strong opioid analgesic, initially 5–10mg over 24 hours, adjusted according to response
    • Adult currently treated with a strong opioid analgesic, click here for a table of approximate equivalent dosages of opioids

Notes

  1. Injectable opioids should not be used in the management of patients with persistent non-cancer pain
  2. Supplies of naloxone injection 400 micrograms in 1ml are required in the same clinical storage locations where diamorphine injections are stored, including in GPs' bags and bags held by out-of-hours providers. (NPSA Safer Practice Notice 12; May 2006)
Morphine sulphate
  • Oral solution 10mg/5ml (£5.45 = 300ml)
  • Tablets 10mg, 20mg, 50mg (£10.61 = 20mg x 56 tablets)
  • Zomorph® m/r capsules 10mg, 30mg, 60mg, 100mg, 200mg (£8.30 = 30mg x 60 capsules)
  • Injection 10mg/1ml, 30mg/1ml (£11.49 = 30mg/1ml x 10 ampoules)
  • Concentrated oral solution 100mg/5ml (palliative care only)
  • MST® m/r tablets 5mg
  • Injection 1mg/1ml, 40mg/1ml preservative free (unlicensed preparation)

Indications

Dose

  • Acute pain (adult doses, for children refer to current cBNF)
    • By subcutaneous injection (not suitable for oedematous patients) or by intramuscular injection, initially 10mg (elderly or frail 5mg) every 4 hours or more frequently during titration), adjusted according to response
    • By slow intravenous injection, initially 5mg (reduce dose in elderly or frail) every 4 hours (or more frequently during titration), adjusted according to response
  • Chronic pain, by mouth initially 5–10mg every 4 hours, adjusted according to response
  • Zomorph® 12 hourly m/r capsules:
    • Every 12 hours, dose adjusted according to daily morphine requirements
    • For breakthrough, doses of 1/6 of the total daily dose of M/R opioid given as immediate release morphine 4-hourly when required
    • During titration any increase in total daily opioid dosage should not be more than 50% of the previous total daily dosage

Notes

  1. Caution, morphine sulphate oral solution may contain alcohol. This may be harmful for those suffering from a history of alcohol dependence and should be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy. Refer to individual Summary of Product Characteristics.
  2. Specify dosing interval on prescriptions to avoid confusion e.g. 4 hourly
  3. Morphine sulphate oral solution should never be prescribed "when required" without a prescribed dose and dose interval
  4. Following titration (except for stat doses e.g. for dressing changes) immediate release morphine should be given regularly every four hours. If pain recurs because of when required dosing it is likely that increased dose or frequency of analgesia may be needed to regain pain control
  5. Zomorph® is the morphine sulphate MR preparation of choice because it is a capsule formulation that may be opened and the contents administered in semi-solid food for patients with swallowing difficulties. MST® lacks these advantages and is more expensive than Zomorph® and so its use is not recommended
  6. Zomorph® is licensed for administration of capsule contents via gastric or gastronomy tubes (diameter greater than 16FG)
  7. Injectable opioids should not be used in the management of patients with persistent non-cancer pain
  8. Supplies of naloxone injection 400 micrograms in 1ml are required in the same clinical storage locations where morphine injections are stored, including in GPs' bags and bags held by out-of-hours providers. (NPSA Safer Practice Notice 12; May 2006)
Buprenorphine
  • Butec® patch 5 microgram/hour for 7 days (£7.92 = 4 patches)
  • Butec® patch 10 microgram/hour for 7 days (£14.20 = 4 patches)
  • Butec® patch 15 microgram/hour for 7 days (£22.12= 4 patches)
  • Butec® patch 20 microgram/hour for 7 days (£25.86 = 4 patches)

Indications

  • Moderate, non-malignant pain unresponsive to non-opioid analgesics

Dose

  • Initially one '5 micrograms/hour' patch; apply to dry, non-irritated, non-hairy skin on upper torso, removing after 7 days and siting replacement patch on a different area (avoid same area for at least 3 weeks)

Notes

  1. If considering for patients with swallowing difficulties, remember that Zomorph® capsules can be opened up for ease of swallowing
  2. Prescribe buprenorphine patches by brand (Butec®) to ensure continuity. High strength buprenorphine patches (Transtec®) are not approved for use.
  3. Buprenorphine patches are not suitable, or licensed, for use in the management of acute or intermittent pain
  4. Prescribers should ensure that patients and/or their careers are aware that Butec® patches need to be applied at appropriate seven-day intervals to ensure that patients are not left in pain (because of too long an interval) and that the patches are not used wastefully (because of too short an interval). Remember to remove the old patch before application of new patch. To increase the dose, a larger patch should replace the patch that is currently being worn, rather than multiple patches being used
  5. Buprenorphine sublingual tablets are not recommended for prescribing in primary care for the management of pain. For their use as an adjunct in the treatment of opioid dependence, refer to section 4.10.3 opioid dependence
Tramadol
  • Capsules 50mg (£2.20 = 100 capsules)
  • Soluble tablets 50mg (£13.33 = 100 tablets)
  • Injection 50mg/ml (£0.98 = 2ml ampoule)

Indications

  • Moderate to severe pain

Dose

  • Oral, 50–100mg not more often than every 4 hours; total of more than 400mg daily not usually required
  • By intramuscular injection or by intravenous injection (over 2–3 minutes) or by intravenous infusion, 50–100mg every 4–6 hours
  • Postoperative pain, 100mg initially then 50mg every 10–20 minutes if necessary during first hour to total maximum 250mg (including initial dose) in first hour, then 50–100mg every 4–6 hours; maximum 600mg daily

Notes

  1. Modified-release preparations of tramadol are non-formulary. However, if there is a defined clinical need for a modified-release preparation, prescribe as 12-hourly brand product Marol® to ensure lowest acquisition cost
  2. Caution: Tramadol increases CNS serotonin levels and may cause increased serotogenic effects when given with other drugs that increase serotonin levels e.g. SSRIs, SNRIs, MAOIs and some TCAs
  3. The CSM have cautioned the use of Tramadol in patients with a history of epilepsy, as there may be an increased risk of convulsions
  4. Injectable opioids should not be used in the management of patients with persistent non-cancer pain
Abstral®
  • Fentanyl sublingual tablets 100 micrograms, 200 micrograms, 300 micrograms, 400 micrograms, 600 micrograms, 800 micrograms (£5.00 = per tablet)

Indications

Dose

Notes

  1. Do not prescribe for patients with non-cancer pain
  2. Following national guidance from NHS England, Abstral® should only be used in patients undergoing palliative care treatment and where the recommendation to use immediate release fentanyl in line with NICE guidance, has been made by a multi-disciplinary team and/or other healthcare professional with a recognised specialism in palliative care
  3. Abstral® should only be used in the minority of patients with breakthrough pain that fail immediate release morphine or oxycodone. Patients must be reviewed weekly
  4. Despite the limited evidence and concerns regarding drug accumulation, fentanyl is a preferred opioid in renal impairment due to its inactive and non-toxic metabolites. It is nevertheless advisable to monitor for signs of opioid toxicity in these patients due to wide inter-patient variability
Effentora®
  • Fentanyl buccal tablets 100 micrograms, 200 micrograms, 400 micrograms, 600 micrograms, 800 micrograms (£4.99 = per tablet)

Indications

Dose

  • Initially 100 micrograms repeated if necessary 30 minutes after first dose (no more than 2 dose units for each pain episode); adjust dose according to response, see titration guidance; maximum 800 micrograms per episode of breakthrough pain; leave at least 4 hours between treatment of episodes of breakthrough pain during titration. Refer to Guidelines for prescribing transmucosal fentanyl preparations for breakthrough pain
  • The dose of Effentora® is not interchangeable with Abstral®, prescribe by brand

Notes

  1. Do not prescribe for patients with non-cancer pain
  2. Following national guidance from NHS England, Effentora® should only be used in patients undergoing palliative care treatment and where the recommendation to use immediate release fentanyl in line with NICE guidance, has been made by a multi-disciplinary team and/or other healthcare professional with a recognised specialism in palliative care
  3. Effentora® should only be used in the minority of patients with breakthrough pain that fail immediate release morphine or oxycodone. Patients must be reviewed weekly
  4. Despite the limited evidence and concerns regarding drug accumulation, fentanyl is a preferred opioid in renal impairment due to its inactive and non-toxic metabolites. It is nevertheless advisable to monitor for signs of opioid toxicity in these patients due to wide inter-patient variability
Transdermal Fentanyl
  • Matrifen® / Mezolar® patch 12 microgram/hour, for 3 days (per patch £1.50)
  • Matrifen® / Mezolar® patch 25 microgram/hour, for 3 days (per patch £2.15)
  • Mezolar® patch 37.5 microgram/hour, for 3 days (per patch £3.09)
  • Matrifen® / Mezolar® patch 50 microgram/hour, for 3 days (per patch £4.02)
  • Matrifen® / Mezolar® patch 75 microgram/hour, for 3 days (per patch £5.61)
  • Matrifen® / Mezolar® patch 100 microgram/hour, for 3 days (per patch £6.91)

Indications

Dose

  • Apply to dry, non-irritated, non-irradiated, non-hairy skin on torso or upper arm, removing after 72 hours and siting replacement patch on a different area (avoid using the same area for several days)
  • Adult and child over 2 years currently treated with a strong opioid analgesic, initial dose based on previous 24-hour opioid requirement. A conversion scheme from oral morphine to fentanyl patches can be found here

Notes

  1. Fentanyl preparations should only be used when initiated/supervised by the specialist pain or palliative care teams.
  2. Prescribers are reminded to prescribe fentanyl by brand to ensure continuity and avoid confusion. Once titrated to an effective dose, patients should not be changed to other forms (matrix or reservoir) of transdermal fentanyl patches.
  3. Do not use in opioid naïve patients. Fentanyl patches should only be used in patients who are opioid tolerant and have already tried a strong opioid such as morphine.
  4. Do not use for acute or intermittent pain.
  5. Ensure that patients and/or their carers are aware that fentanyl patches need to be applied at appropriate 72-hour (three-day) intervals to ensure that patients are not left in pain (because of too long an interval) and that the patches are not used wastefully (because of too short an interval). Remember to remove the old patch before application of new patch. If patient is still experiencing pain in 72 hour change interval, review analgesia options. Do not suggest the patches are changed more frequently.
  6. Fentanyl patches are implicated in a high level of patient harms and the CQC Annual Report for 2012 again highlights the care that must be taken to ensure the safe use of these patches. Fentanyl patches should be restricted to patients that are already receiving regular doses of opioids.
  7. Doses above 25 micrograms/hour are not recommended in the treatment of chronic non-malignant pain (> 3 months). Doses should be regularly reviewed and stepped down as soon as possible. A 25 microgram/hour patch of fentanyl is equivalent to approximately 60-90mg/24 hours of oral morphine (using a dose conversion ratio for morphine to fentanyl of 100-150:1).
  8. Fentanyl patches should not be cut
  9. Despite the limited evidence and concerns regarding drug accumulation, fentanyl is a preferred opioid in renal impairment due to its inactive and non-toxic metabolites. It is nevertheless advisable to monitor for signs of opioid toxicity in these patients due to wide inter-patient variability.
  10. MHRA Drug Safety Update 2008: Serious and fatal overdose of fentanyl patches
    1. healthcare professionals, particularly those who prescribe and dispense fentanyl patches, must fully inform patients and caregivers about directions for safe use
    2. increased body temperature (e.g. fever), exposure of patches to external heat sources (e.g. hot bath or sauna), and concomitant use of CYP3A4 inhibitors may lead to potentially dangerous rises in serum fentanyl levels (examples include: ritonavir, nelfinavir, ketoconazole, itraconazole, clarithromycin, erythromycin, verapamil, diltiazem, and amiodarone) - concomitant use of other CNS depressants might also potentiate adverse effects from fentanyl
    3. healthcare professionals, particularly those who prescribe and dispense fentanyl patches, should ensure that patients and caregivers are aware of the 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
    4. patients who experience serious adverse events should have the patches removed immediately and should be monitored for up to 24 hours after patch removal
  11. MHRA Drug Safety Update 2014 and MHRA Drug Safety Update 2018: Transdermal fentanyl patches: life threatening and fatal opioid toxicity from accidental exposure, particularly in children
    1. Provide clear information to patients and caregivers regarding risk of accidental patch transfer and ingestion of patches, and need for appropriate disposal of patches.
    2. If a patch is transferred to another person, it should be removed and the individual should get medical help immediately.
    3. If a patch is swallowed, the individual should get medical help immediately.
    4. The 2014 drug safety update includes a letter for patients and care givers
  12. Refer to Section 16.2 Transdermal fentanyl patches for further prescribing information.
Oxycodone
  • Shortec® capsules 5mg, 10mg, 20mg (£27.43 = 20mg x 56)
  • Shortec® oral solutionSF 5mg/5ml (£8.25 = 250ml)
  • Longtec® modified release tablets (12 hourly dosing) 5mg, 10mg, 15mg, 20mg, 30mg, 40mg, 60mg, 80mg, 120mg (£38.11 = 30mg x 56)
  • Injection 10mg/ml, 50mg/1ml (£8.00 = 1ml 10mg ampoule x 5)
  • Shortec® oral solution concentrateSF 10mg/1ml (palliative care only)

Indications

  • Moderate to severe pain in patients with cancer
  • Palliative care guidance
  • Postoperative pain
  • Severe non-malignant pain only in patients where morphine is ineffective or not tolerated

Dose

  • Oral immediate release, initially 5mg every 4–6 hours, increased if necessary according to severity of pain, usual maximum 400mg daily, but some patients may require higher doses
  • Oral modified release, initially 10mg every 12 hours, increased if necessary according to severity of pain, usual maximum 200mg every 12 hours, but some patients may require higher doses
  • Slow intravenous injection, 1–10mg every 4 hours when necessary
  • Intravenous infusion, initially 2mg/hour, adjusted according to response
  • Subcutaneous injection, initially 5mg every 4 hours when necessary
  • Subcutaneous infusion, initially 7.5mg/24 hours adjusted according to response

Notes

  1. Oxycodone preparations should only be used when initiated/supervised by the specialist pain or palliative care teams
  2. Injectable opioids should not be used in the management of patients with persistent non-cancer pain
  3. May be used with caution in patients with renal impairment: starting dose should be reduced by 50%. The dose should be slowly titrated upwards depending on response and any observed adverse effects
Targinact®

(combination of oxycodone and naloxone)

  • Tablets modified-release oxycodone/ naloxone 5mg/2.5mg, 10mg/5mg, 20mg/10mg, 40mg/20mg (£84.62 = 20mg/10mg x 56 tablets)

Indications

  • Severe pain requiring opioid analgesia

Dose

  • Adult over 18 years not currently treated with opioid analgesics, initially 10mg/5mg every 12 hours, increased according to response
  • Patients already receiving opioid analgesics can start with a higher dose
  • The maximum daily dose is 80mg/40mg in 24 hours

Notes

  1. Following guidance from NHS England, Targinact® is not to be initiated in primary care. It should only be used when initiated/supervised by the specialist pain, palliative care, or gastroenterology teams, for use in patients where laxative treatment has failed.
  2. There are significantly increased costs and no evidence of benefit of the combination product over other analgesia (with laxatives if necessary)
  3. Not recommended for pre-operative use or within the first 12-24 hours post-operatively
  4. Ensure patients are on full dose of appropriate bowel care prescription before initiating Targinact®
  5. Prescribers should be aware that 60mg of oxycodone in Targinact® is approximately equivalent to 120mg oral morphine. For patients requiring total daily doses above this (e.g. Targinact® 40mg/20mg twice daily), discuss with the specialist pain team
  6. If no clear objective improvement in bowel function is noted, do not continue (measure improvement on Bristol stool Chart)
Tapentadol
  • Tablets MR 50mg, 100mg, 150mg, 200mg, 250mg (£99.64 = 200mg x 56 tablets)

Indications

Dose

  • Initially 50mg every 12 hours, adjusted according to response; maximum 500mg daily

Notes

  1. Tapentadol should only be used when initiated/supervised by the specialist pain or palliative care teams
  2. MHRA Drug Safety Update (January 2019): Tapentadol (Palexia): risk of seizures and reports of serotonin syndrome when co-administered with other medicine
    1. as for all opioid medicines, tapentadol can induce seizures
    2. tapentadol should be prescribed with care in patients with a history of seizure disorders or epilepsy
    3. tapentadol may increase seizure risk in patients taking other medicines that lower seizure threshold, for example, antidepressants such as serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants, and antipsychotics
    4. serotonin syndrome has been reported when tapentadol is used in combination with serotoninergic antidepressants
    5. withdrawal of the serotoninergic medicine, together with supportive symptomatic care, usually brings about a rapid improvement in serotonin syndrome
Alfentanil
  • Injection 500 micrograms/ml, 2ml, 10ml ampoules
  • Injection 5mg/ml, 1ml ampoule

Notes

  1. Intravenous use only by anaesthetists and intensive care physicians due to rapid and profound respiratory depression
  2. Although not included in the original safety alert, the use of 5mg in 1ml amps is subject to the same restrictions as high strength morphine and diamorphine as per NPSA Safer Practice Notice 12; May 2006
Dihydrocodeine
  • Tablets 30mg
  • Tablets m/r 60mg, 90mg, 120mg

Indications

  • Dihydrocodeine is included for the treatment of opioid dependence. Used as second line under specialist initiation and monitoring ONLY if other interventions have failed.
Intravenous Fentanyl
  • Injection 50 micrograms/ml, 2ml, 10ml ampoules
  • Injection 2.5mg in 50ml vials

Notes

  1. Intravenous use by anaesthetists and intensive care physicians only due to rapid and profound respiratory depression. Intravenous fentanyl Patient Controlled Analgesia (PCA) may only be prescribed on the advice of an anaesthetist or the Acute Pain Team
  2. South Devon only: Consult hospital epidural protocol (intranet guideline 0202), Epidural analgesia via continuous infusions
Pethidine

Pethidine produces prompt but short-lasting analgesia; it is less constipating than morphine, but even in high doses is a less potent analgesic. It is not suitable for severe continuing pain. There is a danger of the accumulation of norpethidine with repeated dosing especially in patients who have renal impairment. For these reasons pethidine is not included in the formulary.

 

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