Strong opioid analgesics

MHRA alert: Opioids: risk of dependence and addiction (September 2020).  New recommendations following a review of the risks of dependence and addiction associated with prolonged use of opioid medicines (opioids) for non-cancer pain. Before prescribing opioids, discuss with the patient the risks and features of tolerance, dependence, and addiction, and agree together a treatment strategy and plan for end of treatment
MHRA alert: Benzodiazepines and opioids: reminder of risk of potentially fatal respiratory depression (March 2020)
MHRA advice: Drugs and driving: blood concentration limits to be set for certain controlled drugs in a new legal offence (December 2014) 

Also refer to:

  • SIGN guidance 136 ‘Management of chronic pain’ 
  • Recommendations for the Appropriate Use of Opioids for Persistent Non-Cancer Pain (www.britishpainsociety.org)

Important: Supplementary notes

Table summarising strong opioid analgesic oral and transdermal preparations listed below

  Short-acting (immediate-release) Long-acting (modified-release)
Morphine Sevredol® tablets 10mg, 20mg, 50mg Zomorph® modified-release capsules (twice daily) 10mg,30mg, 60mg, 100mg, 200mg
  Oral solution 10mg/5mL, 100mg/5mL MST Continus® modified-release tablets (twice daily) 5mg, 10mg, 15mg, 30mg, 60mg, 100mg, 200mg
 

MXL® modified-release capsules (once daily) 30mg, 60mg, 90mg, 120mg, 150mg, 200mg

Oxycodone

Shortec® capsules 5mg, 10mg, 20mg Oxypro® modified release tablets 5mg, 10mg, 15mg, 20mg, 30mg, 40mg, 60mg, 80mg
Oral solution 5mg/5mL, 50mg/5mL  

Fentanyl

Abstral® sublingual tablets
100 micrograms, 200 micrograms, 300 micrograms, 400 micrograms, 600 micrograms, 800 micrograms
Matrifen® transdermal patches (72 hour release) 12 micrograms/hour, 25 micrograms/hour,
50 micrograms/hour, 75 micrograms/hour,
100 micrograms/hour
PecFent® nasal spray
100 micrograms/metered spray,
400 micrograms/metered spray
 
Tramadol Capsules 50mg; soluble tablets 50mg modified release capsules (twice daily) 50mg, 100mg, 150mg, 200mg

Opioid conversions – refer to guidance on ‘Choosing and changing opioids’ in Scottish Palliative Care Guidelines.  If in doubt, seek specialist palliative care advice.
Opioid tolerance - if an individual is taking opioids for a chronic non-malignant pain condition, and cannot achieve effective pain relief despite increases in dose, they may be experiencing opioid tolerance; seek specialist advice.
Opioid-induced hyperalgesia (OIH) is a paradoxical response whereby opioid administration induces an increase in pain sensitivity rather than an analgesic effect. The three features felt to be most suggestive of OIH are escalating pain despite increasing opioids, demonstrable hyperalgesia or allodynia and a more diffuse pain distribution away from pre-existing pain sites. Other symptoms of opioid toxicity such as myoclonus, subtle hallucinations may or may not accompany this presentation. Management can involve different approaches including temporary witholding of opioid, dose reduction and/or opioid switching alongside measures to increase elimination of opioid and alternative approaches for breakthrough analgesia. Seek palliative care advice either from PCAS, tel: 01463 705405 or Highland Hospice 24 hour advice line, tel: 01463 243132 or 1333 from Raigmore.
Antiemetics and laxatives – an antiemetic (dopamine antagonist) may be required on initiation of an opioid or on dose increase, however tolerance to nausea occurs within 7 to 10 days. Co-prescribe a combination of a regular stimulant and softening laxative with regular opioid therapy (including weak opioid therapy) for prophylaxis of opioid-induced constipation; refer to Scottish Palliative Care Guidelines and ‘Aid to antiemetic selection’.

 

Note: Following national patient safety reports, Palliative Care recommend that prescriptions for long-acting opioids are written using the approved and brand name to avoid confusion.

Note: Chronic non-malignant pain
• In osteoarthritis the side-effects of strong opioids (oral and transdermal) outweigh any minimal benefits achieved*; local rheumatologists consider that this applies even more so to use in inflammatory joint disease.
*’Oral or transdermal opioids for osteoarthritis of the knee or hip’, Cochrane Database of Systematic Reviews (http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD003115/frame.html).
• There is no clinical evidence for the long-term effectiveness of strong opioids in fibromyalgia, non-specific low back pain, unexplained persistent pain or headaches; avoid use of strong opioids in the treatment of these conditions.

Note: For all health care practitioners who are likely to initiate strong opioids:
1. Perform a comprehensive assessment.
2. Exclude risk of misuse.
3. Discuss risk and benefit.
4. Agree with patients on goal of opioid therapy.
5. Ongoing opioid monitoring.
6. Restrict total oral morphine equivalent dose to less than 120mg/day.
7. Seek specialist opinion if pain not controlled at 120mg/day oral morphine equivalent (hyperalgesia/tolerance)

 

MORPHINE (First Line)

Important: Therapy notes

  • Zomorph capsules are the most cost-effective modified-release morphine sulphate preparation administered every 12 hours. The capsules can be opened and contents mixed with soft food for administration in swallowing difficulties or via enteral tubes greater than 16FG, see SPC.
  • For breathing difficulties and lower dose pain relief, MST 5mg tablets are appropriate.
  • For once daily dosing, MXL capsules are available.

Important: Formulation and dosage details

Formulation:

Oral solution 10mg/5mL (CD schedule 5), 100mg/5mL (CD schedule 2)

Dosage:

By mouth, initially 5 to 15mg in opioid-naïve individuals. Dose will vary according to individual patient requirements: see guidance above.

Important: Formulation and dosage details

Formulation:

Immediate release tablets (CD schedule 2) (Sevredol®) 10mg, 20mg, 50mg

Dosage:

By mouth, initially 5 to 15mg in opioid-naïve individuals. Dose will vary according to individual patient requirements: see guidance above.

Important: Formulation and dosage details

Formulation:

Modified release capsule (Zomorph®) 10mg, 30mg, 60mg, 100mg and 200mg

Dosage:

These capsules can be opened and contents mixed with soft food for administration in swallowing difficulties or via enteral tubes greater than 16FG, see SPC.

Important: Formulation and dosage details

Formulation:

Modified release tablets (twice daily, MST Continus®) (CD schedule 2) 5mg

Dosage:

For lower dose pain relief and breathlessness in palliative care, MST 5mg tablets are appropriate.

Important: Formulation

Modified release capsules (once daily, MXL®) (CD schedule 2) 30mg, 60mg, 90mg, 120mg, 150mg, 200mg

Important: Formulation

Injection (CD schedule 2) 10mg/mL

Important: Formulation

Intravenous infusion (CD schedule 2) 50mg/50mL

OXYCODONE

Important: Therapy notes


This is a second-line, strong opioid, therefore consideration to morphine equivalents and relevant modifying clinical requirements, eg renal function to be considered. 

Important: Formulation and dosage details

Formulation:

Capsules immediate-release (Shortec®) (CD schedule 2) 5mg, 10mg, 20mg

Dosage:

By mouth: initially in opioid-naïve individuals:
(Shortec) 2mg to 5mg every 4 hours as required

Important: Formulation and dosage details

Formulation:

Modified release tablets (Oxypro®) (CD schedule 2) 5mg, 10mg, 15mg, 20mg, 30mg, 40mg, 60mg, 80mg

Dosage:

By mouth: initially in opioid-naïve individuals:
(Oxypro) 10mg to 20mg every 12 hours

Important: Formulation and dosage details

Formulation:

Oral solution (CD schedule 2) 5mg/5mL, 50mg/5mL

Dosage:

By mouth: initially in opioid-naïve individuals:
(Oral solution) 2mg to 5mg every 4 hours as required

Important: Formulation

Injection (CD schedule 2) 10mg/mL, 20mg/2mL, 50mg/mL

TRAMADOL

Important: Therapy notes

Note: Tramadol has a mixed mode of action but still displays some of the opioid side-effects.
• It can still cause respiratory depression.
• It reduces the seizure threshold; take care with patients who abuse alcohol and those with epilepsy.
• There is a risk of serotonin syndrome when tramadol is used in combination with other serotonergic drugs like antidepressants. Take particular care with MAOIs to avoid concomitant use and for 2 weeks after stopping; refer to BNF for full list of interactions.
• Avoid concomitant use with other opioids.
• To avoid withdrawal symptoms following treatment for longer than 1 month, gradual dose reduction is recommended. Seek specialist advice.
• Modified release capsules and soluble tablets are considerably more expensive than the 50mg capsules.

Important: Formulation and dosage details

Formulation:

Capsules (CD schedule 3) 50mg

Dosage:

Chronic non-malignant pain: Capsules and soluble tablets: 50mg to 100mg, no more often than every 4 hours, maximum 400mg daily.

Important: Formulation and dosage details

Formulation:

Soluble tablets (CD schedule 3) 50mg

Dosage:

Chronic non-malignant pain: Capsules and soluble tablets: 50mg to 100mg, no more often than every 4 hours, maximum 400mg daily.

Important: Formulation and dosage details

Formulation:

Modified release capsules(CD Schedule 3) (twice daily) 50mg, 100mg, 150mg, 200mg

Dosage:

Chronic non-malignant pain: Modified release capsules: 50mg to 200mg twice daily, maximum 400mg daily.

Important: Formulation

Injection (CD schedule 3) 100mg/2mL (specialist use by anaesthetists only)

FENTANYL

Important: Therapy notes

MHRA alert: Transdermal fentanyl patches for non-cancer pain: do not use in opioid-naive patients (September 2020) (www.gov.uk).
MHRA alert: Transdermal fentanyl patches: life-threatening and fatal opioid toxicity from accidental exposure, particularly in children (October 2018) (www.gov.uk)
MHRA alert: Serious and fatal overdose of fentanyl patches (December 2014) (www.gov.uk).

Risk minimisation materials:

  • Actiq: Patient Guide, Patient Treatment Diary and Prescription Guide for Health Care Professionals
  • Instanyl: Single Dose Nasal Spray Patient's Guide. Pharmacist's Guide for dispensing and Physician's Guide for prescribing.
  • Matrifen Transdermal Patches, information for Health Care Professionals. 

Important: Formulation and dosage details

Formulation:

Sublingual tablets immediate release (Abstral®) (CD schedule 2) 100 micrograms, 200 micrograms, 300 micrograms, 400 micrograms, 600 micrograms, 800 micrograms (s)

Dosage:

Breakthrough pain in patients using opioid therapy for chronic cancer pain only: PecFent and Abstral are rapid acting preparations. Their prescription should only be initiated by a specialist in palliative care.

Important: Formulation and dosage details

Formulation:

Nasal spray immediate release (PecFent®) (CD schedule 2) 100 micrograms/metered spray, 400 micrograms/metered spray (s)

Dosage:

Breakthrough pain in patients using opioid therapy for chronic cancer pain only: PecFent and Abstral are rapid acting preparations. Their prescription should only be initiated by a specialist in palliative care.

Important: Formulation and dosage details

Formulation:

Transdermal patches 72-hour release (Matrifen®) (CD schedule 2) 12 micrograms/hour, 25 micrograms/hour, 50 micrograms/hour, 75 micrograms/hour, 100 micrograms/hour

Dosage:

Transdermal: only use if oral opioid/analgesic requirements are stable.
In chronic non-malignant pain, if patch requirements are above 50 micrograms/hour, refer the patient for a specialist opinion as unlikely to benefit beyond this dose. 

Important: Formulation

Injection (CD schedule 2) 100 micrograms/2mL, 500 micrograms/10mL

DIAMORPHINE (First Line)

Important: Therapy notes

Diamorphine is more soluble than morphine and reduces the volume of administration of the injection. It is administered by subcutaneous injection or continuous subcutaneous infusion in chronic cancer pain.  The subcutaneous route is less invasive, more comfortable and less painful than other parenteral routes and has 100% bioavailability.

 

Important: Formulation and dosage details

Formulation:

Injection (CD schedule 2) 5mg, 10mg, 30mg, 100mg

Dosage:

Refer to local guidance. Dose should be one third of the corresponding oral morphine dose, eg for a total daily dose of oral morphine 30mg, change to continuous subcutaneous infusion of diamorphine 10mg daily. For doses above 100 to 120mg consider specialist advice. See guidance on epidural use.

Notes:

There is currently a shortage of diamorphine, please refer to the medicines shortage log  (NHS Highland intranet access required).

METHADONE

Important: Therapy notes

MHRA advice: Drugs and driving: blood concentration limits to be set for certain controlled drugs in a new legal offence (December 2014) (www.gov.uk)

Important: Formulation and dosage details

Formulation:

Tablets (CD schedule 2) 5mg (specialist recommendation)

Dosage:

Only for initiation under the guidance of a palliative care or chronic pain specialist

Important: Formulation and dosage details

Formulation:

Injection (CD schedule 2) 10mg/1mL (specialist recommendation)

Dosage:

Only for initiation under the guidance of a palliative care or chronic pain specialist.

PETHIDINE

Important: Therapy notes

Important: Formulation and dosage details

Formulation:

Injection (CD schedule 2) 50mg/1mL (s)

Dosage:

Management of rigors in patients receiving treatment with monoclonal antibodies off-label.

TAPENTADOL

Important: Therapy notes

MHRA advice: Tapentadol (Palexia): risk of seizures and reports of serotonin syndrome when co-administered with other medicines (January 2019) (www.gov.uk)

Important: Formulation and dosage details

Formulation:

Modified release tablets, (twice daily Palexia SR®) (CD schedule 2) 50mg, 100mg, 150mg, 200mg, 250mg (specialist recommendation) 

Dosage:

for initiation by or on the advice of a chronic pain consultant only.