Opioids

Summary of recommendations: opioids

 

Indications and effectiveness

Summary:

• Opioids should not be considered routinely for people with chronic non-malignant pain. In carefully selected individuals, when other therapies have been fully explored, opioids can be considered for short-term treatment (up to three months), if it is considered that the potential benefits outweigh the risks of serious harms such as addiction, overdose and death^{37,53,58,59,60,61,62,63,64}
• The benefits of opioids in chronic pain are limited to lower doses for short to medium-term treatment (less than three months)
• There is some evidence for intermittent use of weaker opioids g. codeine or dihydrocodeine on a when required basis, especially if a particular activity/scenario causes a short term increase in pain⁴⁷

Generally:

• Prescribers should consider the risks and harms against the benefits of taking opioids⁶¹
• Individual review is recommended within four weeks of starting opioid treatment or sooner if required⁶⁵
• Individuals should be informed that if pain remains severe despite opioid treatment, this indicates that the opioid is not working and should be stopped, even if no other treatment is available⁶⁶
• The frequency of review once the opioid regimen is established depends on individual factors, but should be at least, annually⁶⁵ to identify possible harms and consider the effectiveness of treatment
• All people on an opioid should have a review of their treatment, prioritising individuals prescribed more than 50mg morphine equivalent dose (MED), who should be reviewed at least annually to consider ongoing effectiveness and potential harms, due to lack of evidence to support long-term use.^65,67,68 See opioid dose conversion chart below
• Higher doses of opioids have a greater risk of serious harm with no additional benefit:
  • 50-100mg MED, has a four times higher risk than less than 50mg MED
  • Greater than 100mg MED has a nine times higher risk
  • Serious harms include inappropriate opioid use, overdose and death, increased risk for falls and major trauma, and increased likelihood of road accidents65
• Due to tolerance developing, the analgesic effect of opioids lessens over time and individuals require higher doses to maintain the same level of pain relief^69,65,70
• If a change from one opioid to another is required, the relative potency should be accounted for and dose equivalence charts used (see opioid dose conversion chart below). Particular caution is required with fentanyl due to its high potency
• If the decision has been agreed to prescribe an opioid for an individual with chronic pain it is good practice to agree an individualised treatment plan, which sets realistic goals, highlights potential side effects and risks and sets criteria for stopping the opioid. For more details, see opioid dose conversion chart below
• Where possible, the usefulness of opioids should be explored by prescribing a short trial (one-to-two-week supply) of immediate release morphine tablets or liquid and reviewing to assess the response

Morphine:

• Individuals should be considered as opioid non-responsive if 20mg of immediate-release morphine does not reduce pain intensity
• As there is no evidence of difference in pain control between opioids, morphine is the preferred cost-effective option when a stronger opioid is required¹⁸
• As more evidence is available, the accepted upper dosage limits are being reviewed and reduced. Current recommendations indicate the upper dosage levels should be less than 50mg to minimise longer term risks and adverse effects, and previous upper limits of 90mg to 120mg should be reviewed
• It is good practice to not prescribe more than 90mg/day MED without seeking advice from prescriber specialising in pain
• It is good practice to use extreme caution when prescribing more than 120mg/day MED due to the risk of harm substantially increasing at these doses.⁶⁵ Please note this does not apply when prescribed in palliative care and post-operative care

Tramadol:

• Has high potential for drug interactions. A MHRA Drug Safety Update highlighted the risk of increased International Normalised Ratio (INR) when warfarin and tramadol are used together, with a risk of major bruising and bleeding which could be life-threatening.
• It is good practice not to combine with other opioids for mild to moderate pain
• One study considered tramadol as suitable for neuropathic pain⁷¹, however another found no significant difference between it and placebo⁵⁹
• Tramadol and paracetamol combination product are not recommended by the SMC for use within Scotland for the symptomatic treatment of moderate to severe pain

Other opioids

• Transdermal buprenorphine or fentanyl could be an option for treatment when there are reasons prohibiting oral administration

Fentanyl:

• other analgesics and other opioids for non-malignant pain should be trialled before prescribing fentanyl patches
• due to the potency of fentanyl the use of transdermal patches is contra-indicated in opioid-naive individuals
• the use of immediate release fentanyl is not recommended as it is restricted for use for the management of breakthrough pain in adults using opioid therapy for chronic cancer pain, when other short-acting opioids are unsuitable
• is suitable in renal impairment and use with caution⁷²

Buprenorphine:

• is an alternative for those with renal dysfunction (even severe)
• patches are available in several brands. They are available in different strengths and are not all interchangeable therefore buprenorphine patches should be prescribed by brand name
• patches are not appropriate for individuals with acute pain and those who need rapid dose escalation
• Seven-day transdermal patches (5 to 20 micrograms) should be prescribed in line with SMC restriction: For use in elderly individuals (over 65 years) for the treatment of non-malignant pain of moderate intensity when an opioid is necessary for obtaining adequate analgesia 

Oxycodone:

• requires dose adjustment in renal impairment
• oxycodone and naloxone combination prolonged released tablets are not recommended by SMC

Risks and harms

• Risks can be categorised by the timescale on which they may be seen, although some can occur in any timeframe.
  • Short-term:
    • drowsiness, dizziness, confusion
    • constipation, nausea/vomiting
    • respiratory depression
  • Long-term:
    • dependence and addiction, even at therapeutic doses, following prolonged use (longer than three months)⁴²
    • may adversely affect the immune system (immunosuppression)⁷³
    • increased risk of myocardial infarction and cardiovascular revascularisation⁷³
    • hyperalgesia⁷⁴ – which is increased pain sensitivity
    • adrenal insufficiency
    • sexual dysfunction, fatigue and decreased levels of testosterone (in men and in women)^75,76
  • Additional factors to consider during any timeframe:
    • risk of overdose, problematic substance use, dependence, diversion
    • interactions with other CNS depressant (such as anticonvulsants, benzodiazepines, gabapentinoids), with increased risk of respiratory depression and overdose ^77,78,79
    • Increased fracture risk

• Individuals who require particular consideration to minimise the risk of harm include:
  • History of problem substance use
  • Renal impairment
  • Recently discharged following surgery
  • Older/frail
• The risks of dependence are increased in individuals with current or history of problem substance use (including alcohol) or mental health conditions (for example, major depression). Additional support and monitoring may be necessary when prescribing for individuals at risk of inappropriate opioid use.⁴²

In 2014, the Medicines and Healthcare products Regulatory Agency (MHRA) highlighted the risk of inadvertent exposure to fentanyl patches, emphasising the need for providing information to patients and caregivers regarding the safe handling of patches and safe disposal of used and unused patches.   

Prescribers should consider the adverse effects against the limited long-term benefits, as there are few trials examining the efficacy of long-term opioid use (≥3 months) in those with chronic pain. There are limited numbers of studies of variable quality which demonstrate long-term efficacy.^61,65,68

Mitigation of harms and reduction of known adverse effects

Laxatives:

• Constipation is common even with low dose weak opioids. Laxatives should be considered when initially prescribing opioids, with a stimulant and softener being first choice, and continued if necessary on a regular basis.

Naloxone:

• Respiratory depression can occur, either with acute higher doses, or lower doses in at risk individuals. Naloxone is commonly used in substitution therapy, however its use to mitigate against respiratory depression in general medicine is an emerging area of understanding.
• Prior to prescribing naloxone, other means to reduce the risk of respiratory depression should be employed. This may include medication review, to reduce opioid dose or deprescribing of other medications which contribute to the risk (see polypharmacy triple whammy section later).
• Clinicians should consider prescribing naloxone for those prescribed an opioid and who may be at risk of an opioid overdose.⁸⁰ Take-Home Naloxone Programme is available across all boards in Scotland. The naloxone website has information on how to spot signs of overdose and how to administer naloxone.