Assessment

• Thorough clinical assessment including: site, character, radiation, exacerbating or relieving factors, timing and severity (see Table 8.1 for further details).
  
• On average cancer patients experience two distinct pains, so documentation of individual pains must be made.
  
• Full medication history, including topical, inhaled, as required and over-the-counter or complementary therapies. Establish which medications patients feel have been effective for their symptoms and any side effects experienced, as this affects adherence.
  
• Establish which medications patients have also tried that were ineffective and why.

Choice of analgesic

• The World Health Organisation (WHO) analgesic ladder (see Figure 8.1) provides the basis for initiating and titrating analgesia. It considers the severity of pain and previous analgesia. Start at the step appropriate for the patient’s level of pain.
  
  
  
  • Simple analgesics include paracetamol and NSAIDs.
    
  • Weak opioids refer to codeine and tramadol. Strong opioids include morphine, oxycodone, fentanyl and buprenorphine. Strong opioids are indicated if pain is moderate to severe in intensity or if pain has not responded to weaker analgesia.
    
  • Adjuvant medications are drugs which were not originally marketed for pain but have been found to be effective in certain situations, for example antidepressants and anticonvulsants for neuropathic pain and bisphosphonates for bone pain.
  
  
• Paracetamol should be prescribed in all patients unless there is a contraindication. It has a synergistic effect with opioids. The dose may need to be reduced with liver impairment or in patients weighing less than 50 kg.
  
• NSAIDs are indicated for pain with an inflammatory component or bone pain, but have serious side effects, including gastric ulceration or bleeding and renal impairment:
  
  
  
  • Patients on steroids already have a higher risk of GI problems. Concomitant aspirin and SSRIs also greatly increase the risk of bleeding.
    
  • Palliative care patients may have pre-existing renal impairment which can be exacerbated, so renal function should be monitored and NSAIDs used with caution.
    
  • Consider starting a PPI concurrently.
    
  • Ibuprofen: 400 mg every 8 hours (max 2.4 g in 24 hours, but 1.2 g in 24 hours is usually sufficient for maintenance) is the safest NSAID in terms of GI and cardiovascular toxicity. Consider the risks and benefits on an individual basis.
    
  • Newer COX-2 selective NSAIDs can be given once daily, so reduce tablet burden, but have increased cardiovascular risks; therefore risk of stroke or MI should be balanced against potential benefit, even with short-term use.
    
  • The important message when prescribing an NSAID is to evaluate patients individually and consider their risk of GI, renal and cardiovascular complications.
  
  
• Weak opioids: codeine 30–60 mg QDS is an effective step 2 analgesic and should be co-prescribed with paracetamol. A combination preparation is available (co-codamol 30/500 mg) which reduces tablet burden. Codeine is metabolised to morphine via CYP2D6; however, it is not metabolised (and therefore ineffective) in up to 10% of people, and can be constipating and cause nausea which can limit the useful dose. See the opioid prescribing section for more details.
  
• Strong opioids: see the opioid prescribing section for more details.
  
• Adjuvants: these include antidepressants, anti-epileptics and bisphosphonates. Examples include gabapentin, amitriptyline and pregabalin for neuropathic pain:
  
  
  
  • These can cause drowsiness so need to be titrated and monitored closely. They should be started by a senior doctor or by those with specialist knowledge, such as the palliative care and pain team.
    
  • Gabapentin is started at a dose of 300 mg nocte and titrated upwards (increase by 300 mg a day) to a maximum of 600 mg TDS.
    
  • Pregabalin is started at 75 mg nocte and titrated upwards to a maximum of 300 mg BD.
    
  • Amitriptyline is started at 10 mg nocte and titrated gradually every 5–7 days up to 75 mg. Higher doses (up to 150 mg/day) may be used following specialist advice, but are associated with side effects that outweigh their analgesic benefit. Patients should be advised that sleepiness can persist to the next morning and may impair their ability to drive.

Renal and liver failure

• Liver failure: morphine is relatively safe in liver failure, but metabolites may accumulate, paracetamol should be reviewed and patients may need a dose reduction.
  
• Renal failure:
  
  
  
  • Morphine can accumulate quickly in those with renal failure as it is renally excreted.
    
  • Oxycodone has less toxic metabolites and patients with a mild level of impairment may be started on or switched to oxycodone.
    
  • Alfentanil does not rely on renal excretion and therefore is useful in patients in renal failure. As it has a very short half-life it should be given as a continuous infusion:
    
    
    
    • To convert oral morphine doses to alfentanil the 24-hour dose should be divided by 30.
      
    • The breakthrough analgesia in those with severe renal impairment who have an alfentanil infusion should be oxycodone (as alfentanil is very short acting).
      
    • Alfentanil does not accumulate and is not removed by dialysis.
    
    
  • Buprenorphine and fentanyl can also be used.
  
  
• In renal impairment and end-stage renal failure, regardless of the opioid used, extra caution is always required whether or not the patient is on dialysis. This is particularly necessary in patients with rapidly deteriorating renal function or when acutely unwell.
  
• NSAIDs are generally avoided in renal failure. However, if a patient’s pain is due to bony metastases and other inflammatory processes, which may respond to NSAIDs, cautious use with monitoring of renal function can be trialled if alternative analgesia is ineffective.

Bone pain

Bone pain can be managed with radiotherapy, bisphosphonates and NSAIDs (see section on NSAIDs above). Following treatment with bisphosphonates or radiotherapy pain may improve dramatically, sometimes allowing a reduction in the doses of regular analgesia.

General principles of opioid prescribing

• There is no maximum dose of opioid, but if patients are requiring very high doses re-assess the pain and consider reversible causes or whether the pain is non-responsive to opioids.
  
• Do not prescribe more than one opioid at a time.
  
• Ensure an immediate release opioid for episodes of breakthrough pain is prescribed and patients know that they can take these medications in addition to any regular modified release preparations to control pain (see the initiating strong opioids section for details on how to calculate breakthrough doses).