Pharmacological management

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Cancer pain management in adults > Pharmacological management
Contents Introduction Recommendations Overview Patient-centred care Screening Assessment
Self-management Pharmacological Mx Non-pharmacological Mx Practice improvement Resources Opioid formulations References

Information on authorship and revision

Page last modified: 6 May 2016 09:17:05

Author(s): Australian Adult Cancer Pain Management Working Group


Pharmacological management


Warning! Please refer to Approved Product information before prescribing any agent discussed in this guideline


Warning! Perform comprehensive assessment and reassess efficacy and adverse effects


Warning! Exclude causes other than cancer before commencing opioid therapy for pain - see comprehensive assessment


Warning! Dose reduction and regular re-assessment may be needed for elderly or frail patients


Note Use the eviQ Opioid Conversion Calculator for calculating dose equivalents for opioid preparations available in Australia. Note that users need to set up a free account to access this tool

Regular analgesia

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P1. For patients with continuing pain, begin regular analgesia with paracetamol and/or a nonsteroidal anti-inflammatory drug (NSAID) if the patient has no contraindications. (ESMO, NCCN, SIGN)
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P2. If pain is moderate or severe or continues despite treatment with paracetamol or NSAIDs, consider a regular oral opioid. (EAPC,ESMO,NCCN)

• For patients with normal renal and hepatic function, start with a low dose (e.g. morphine 20–30 mg per day [10-15 mg sustained release every 12 hours or 5 mg immediate release every 4 hours] with 5 mg immediate release rescue doses 1 hourly as needed for breakthrough pain.

• In elderly or frail patients, starting doses should be half the above doses.

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P3. If pain continues or recurs despite regular oral opioid analgesia and the patient feels that analgesia is inadequate, consider either of the following options:

• Add a NSAID (if the person is not already taking a NSAID and has no contraindications). (EAPC)

• Increase regular dose of opioid to incorporate the rescue doses taken in previous 24 hours (SIGN), then reassess pain severity and adverse effects within 48 hours. (Consensus)

Care should be taken when calculating a new regular dose for patients who are pain free at rest but have pain on movement (incident pain). If all the analgesia for this pain is incorporated into the new regular morphine dose, such patients could be rendered opioid toxic. In particular, they will be rendered excessively sleepy at rest. This is because pain is a physiological antagonist to the sedative and respiratory depressant side effects of opioids. In such cases, optimum analgesia is achieved by maximising background analgesia, pre-emptive analgesia for movement related pain, maximising non-opioid and adjuvant analgesics and consideration of other treatment modalities such as radiotherapy, anaesthetic nerve blocks, and stabilising surgery. (SIGN)

expand arrowSample calculation
A patient taking 5 mg morphine q4h requires three extra 5 mg rescue doses for breakthrough pain. The resulting total 24-hour dose is 45 mg morphine. The new regular analgesic regimen is morphine 7.5 mg q4h, with a new rescue dose of 7.5 mg.


Note Cyclooxygenase-2 selective inhibitors (eg celecoxib, etoricoxib, lumiracoxib and parecoxib) produce fewer gastrointestinal symptoms and clinically important ulcer complications than traditional NSAIDs although these can still cause serious and sometimes fatal GI reactions. (SIGN)

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P4. Methadone should be initiated and titrated only by specialists familiar with its use. (EAPC, ESMO, NCCN)
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P5. The transdermal route of administration can be considered as an alternative to oral administration if required, for patients unable to take oral medications, reduced risk of constipation with transdermal preparations, where lack of access to regular administration of other opioids acts as a barrier to pain management, or patient convenience. (EAPC) Due to the slow onset of effect and long duration of action, the transdermal route should be considered only when pain is stable. (ESMO, NCCN, SIGN)

Use one of the following options, referring to the eviQ Opioid Conversion Calculator:

• Switch to transdermal buprenorphine (suitable for patients with stable mild pain only). (NICE) Note: A 20 mcg/hour buprenorphine transdermal patch is equivalent to 30 mg morphine daily orally.

• Switch to transdermal fentanyl. (NICE) Note: The lowest dose available (12 mcg/hour) for fentanyl transdermal patch is equivalent to 45 mg morphine daily orally.


Note In hot climates, the rate of transdermal absorption can be affected by fever, sweating and poor patch adherence to the skin


Warning! Before prescribing opioids, check renal function and titrate dose accordingly. See renal impairment for information about pain management where renal function is compromised.


Warning! NSAIDs are associated with gastrointestinal, cardiovascular and renal adverse effects and should be used with caution, particular in patients aged over 65 years. Gastrointestinal risk is increased in patients with a past history of upper gastrointestinal tract bleeding , NSAID-related ulcer or Helicobacter pylori infection. Cardiovascular risk is increased in patients with other cardiovascular risk factors. Risk of renal impairment is increased in patients with pre-existing renal impairment, chronic heart failure or cirrhosis and in those taking diuretics, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, aspirin or other nephrotoxic drugs, and in patients on a salt-reduced diet.


Note Provide information and education for patients and carers about cancer pain management, including the benefits and risks of opioid medicines. (Patients and health professionals commonly have concerns about addiction, tolerance and dependence that are disproportionate to the risks.) See also Self-management section.


Note If the prescribing clinician or other staff are unfamiliar with an analgesic agent under consideration, consult a specialist pain medicine physician, palliative medicine physician, clinical pharmacist or clinical pharmacologist who are familiar with the use of the agent.


Note For all opioids listed on the PBS, one month's supply can be obtained via a telephone extended prescription authorisation from the PBS. Prescribing one month at a time is recommended once pain is stable.


Note For patients with a specific pain syndrome, consider an adjuvant.

Preventing, monitoring and managing adverse effects of opioids

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Renal impairment

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P6. For patients with renal impairment (calculated creatinine clearance 30-90ml/min), carefully monitor for treatment-related adverse effects. If opioid-related adverse effects occur, consider the following options:

• Reduce the total 24-hour dose of regular opioid (either by reducing dose and maintaining dose interval, or increasing dose interval and maintaining dose). (ESMO, SIGN)

• Switch from sustained release to immediate release opioid at an appropriate regular dosing interval. (SIGN)

• Switch to a different opioid (e.g. consider buprenorphine or fentanyl instead of morphine, codeine or hydromorphone) or methadone under specialist supervision. (EAPC, ESMO, NCCN, SIGN)

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P7. Morphine is not recommended for patients with severe (stage 4-5) kidney disease (calculated creatinine clearance of less than 30 mL/minute) due to accumulation of active metabolites and opioid toxicity. (EAPC, SIGN)

Buprenorphine, fentanyl, hydromorphone or oxycodone are preferred opioids in severe kidney disease. Codeine, a weak opioid often chosen as step 2 on the World Health Organisation (WHO) Cancer Pain Ladder, is metabolised to morphine derivatives within the body and should therefore also be avoided in kidney disease. An alternative weak opioid, Tramadol, can be used with a maximal dose of 50-100mg bd in patients with a calculated creatinine clearance of 10-30ml/min or 50mg bd if creatinine clearance <10ml/min and undergoing dialysis. Tramadol is dialysed out, so doses should be given post-dialysis.(Consensus) expand arrow

Davison SN, Koncicki H, Brennan F. Pain in Chronic Kidney disease- a Scoping review, Seminars in Dialysis 2014; 27: 188-204


Note Fentanyl can be used in patients with severe renal impairment, including patients on dialysis.


Note Switch to a different opioid under specialist advice (e.g. sufentanil, methadone).


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Additional prescribed analgesic for breakthrough pain

Breakthrough pain is pain of moderate or severe intensity arising on a background of controlled chronic pain. Breakthrough pain may be described as spontaneous (unexpected) or incident (expected or predictable). (SIGN)

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P8. In addition to regular opioids, routinely prescribe short-acting opioids at a dose equivalent to one-sixth of total 24-hour dose, to be administered if breakthrough pain occurs. (NHS, SIGN) Rescue doses should be prescribed at 1-hourly intervals when required (NCCN) with advice given for the patient to seek health care professional advice if 3 consecutive doses have not relieved pain. (Consensus)
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P9. If breakthrough pain occurs, monitor the number of breakthrough doses. If rescue analgesic doses have been effective with no adverse effects, re-titrate the regular opioid 24-hour dose by calculating the previous 24 hour opioid requirement including breakthrough doses. (SIGN) Note - if breakthrough analgesia is taken preemptively for incident pain, then the regular dose may not need to be increased.
expand arrow Sample calculation
A patient taking 5 mg morphine q4h requires three extra 5 mg rescue doses for breakthrough pain. The resulting total 24-hour dose is 45 mg morphine. The new regular analgesic regimen is morphine 7.5 mg q4h, with a new rescue dose of 7.5 mg.
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P10. If the person experiences incident pain on a background of stable pain control while taking regular opioids, give additional oral short-acting opioids at a dose equivalent to one-sixth of total 24-hour dose. Transmucosal fentanyl preparations may be of use and require individual titration.(NHS, SIGN, EAPC)
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P11. If the person experiences incident pain (e.g. movement-related pain or pain with dressing changes), advise him/her to take preemptive analgesia 30 minutes before activity that is likely to cause pain. (EAPC, NCCN, NHS, SIGN)
expand arrow Sample calculation
A patient taking 5 mg morphine q4h requires three extra 5 mg rescue doses for breakthrough pain. The resulting total 24-hour dose is 45 mg morphine. The new regular analgesic regimen is morphine 7.5 mg q4h, with a new rescue dose of 7.5 mg.


Note Nerve blocks can be considered for refractory incident pain.


Note Transmucosal fentanyl (i.e. lozenges) is not recommended as first-line treatment for breakthrough pain.

More information about re-titrating the opioid dose for breakthrough pain under #Regular analgesia.

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Adjuvants

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P12. For patients with neuropathic pain that persists despite non-opioid and opioid analgesia consider the following options (EAPC, ESMO, NCCN, SIGN):

• Anticonvulsant agents (gabapentin or pregabalin)
• Antidepressants (amitriptyline, nortriptyline or venlafaxine).


Note For anticonvulsants, start at a low dose and titrate according to benefit and adverse effects.


Note Pregabalin is available on the PBS. Gabapentin is not reimbursed by PBS for use in pain management. Self-funding may be expensive.


Warning! Carbamazepine is not registered for the management of neuropathic pain due to cancer, has haematological adverse effects and may interfere with chemotherapy.


Note If the prescribing clinician or other staff are unfamiliar with an adjuvant agent under consideration, consult a specialist pain medicine physician, palliative medicine physician, clinical pharmacist or clinical pharmacologist who are familiar with the use of the agent.


Note If pain persists despite an adjuvant, refer for specialist advice as interventional techniques. may be of value.

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P13. For patients with bone metastases consider bisphosphonates for prevention of bone pain. (ESMO, NCCN, NHS, SIGN)
expand arrow Update
Systematic review by: Porta-Sales J, Garzon-Rodriguez C, Llorens-Torrome S, Brunelli C, Pigni A, Caraceni A. Evidence on the analgesic role of bisphosphonates and denosumab in the treatment of pain due to bone metastases: A systematic review within the European Association for Palliative Care guidelines project. Palliat Med. 2016 Mar 22.


Warning! Bisphosphonates should be prescribed with caution in patients with renal impairment.


Warning! Bisphosphonates have been associated with osteonecrosis of the jaw. The risk is increased after dental extractions and by periodontal disease. The Therapeutic Goods Administration (Australian Government Department of Health and Ageing) encourages health professionals prescribing bisphosphonates to:

• consider dental referral of the patient before starting treatment, especially for people at increased risk, such as the elderly

• reinforce the importance of good oral hygiene

• inform patients of the symptoms of osteonecrosis of the jaw that may occur while taking or after being given a bisphosphonates, such as "toothache" or pain, swelling or numbness of an area of the jaw or a discharge around a dental implant

• advise their patients that they should notify their dentist that they are taking or have been given a bisphosphonates. [See http://www.tga.gov.au/safety/alerts-medicine-bisphosphonate-071211.htm]

info
Bisphosphonate TGA-approved Australian indications include:
Disodium pamidronate Treatment of tumour-induced hypercalcaemia

Treatment of predominantly lytic bone metastases from breast cancer, advanced multiple myeloma

Ibandronate sodium Treatment of metastatic bone disease in patients with breast cancer (tablets, injection)

Treatment of tumour-induced hypercalcaemia, with or without metastases (injection)

Sodium clodronate Treatment of hypercalcaemia of malignancy

Treatment of osteolytic lesions (breast cancer metastases, multiple myeloma)

Zoledronic acid Treatment of tumour-induced hypercalcaemia

Prevention of skeletal related events in advanced malignancy involving bone

TGA: Therapeutic Goods Administration

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Anti-cancer treatment

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P14. For patients with painful bone metastases, consider single-fraction radiotherapy or radioisotopes. (ESMO, NCCN, NHS, SIGN)
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P15. Consider denosumab for preventing skeletal events and bone pain from metastatic breast or prostate cancer.

(NCCN)


Warning! Denosumab is associated with increased risk of hypocalcaemia. The starting dose should be low and reassessed after 1 week.


Warning! Denosumab is associated with osteonecrosis of the jaw. Dental review is recommended before and after starting denosumab treatment. Supplement with calcium and Vitamin D for patients who are not hypercalcaemic.


Note Denosumab (RANK ligand monoclonal antibody) is registered in Australia for the treatment of skeletal-related events in patients with bone metastases from solid tumours. It is listed on the PBS for the treatment of bone metastases in patients with breast cancer or hormone resistant prostate cancer.


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Interventional therapy

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P16. For patients with refractory pain despite carefully titrated doses of conventional medical therapies, consider whether a spinal route of administration may be indicated. (NCCN, NHS, SIGN)
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P17. Consider nerve blocks for selected pain syndromes (e.g. coeliac plexus block for pain in pancreas or upper abdomen). (NCCN)
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P18. Consider intrathecal infusion of analgesic for patients with any of the following:

• difficult-to-control pain (EAPC)

• diffuse pain (NCCN)

• unacceptable opioid-related toxicity despite optimal use of adjuvants and a trial of switching opioids. (SIGN)

Refer to a specialist pain medicine physician or palliative medicine physician.


More information about opioid switching.

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Preventing, monitoring and managing adverse effects of opioids

Routine prevention of adverse effects and education

Note Explain to patients starting opioids that constipation is a very common side effect, and provide education about preventative bowel care.


Note Provide patients with information about the prevalence of opioid-related emesis and education about non-pharmacological management (e.g. avoiding strong smells).


Note Ensure adequate mouth care for all patients receiving opioids.


Note Explain to patients starting opioid treatment that they may experience nightmares.

More information about Self-management

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Assessment and management of opioid toxicity and adverse effects

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P19. Reduce the risk of constipation in non-terminal patients by using all of the following strategies:

• Maintain adequate hydration. (NCCN)

• Encourage physical activity (ambulant patients). (NCCN)

• Provide education on bowel hygiene routine (e.g. dietary fibre). (Consensus)

• Use a combination of stimulant and softening laxatives (EAPC, NCCN, NICE, SIGN)

• Avoid other medicines that can aggravate constipation (e.g. 5HT3 antagonists) if possible. (Consensus)

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P20. For an ambulant non-terminal patient with critical constipation caused by opioids that is not responding to oral stimulant and softening laxatives or polyethylene glycol (NCCN), consider one of the following options:

• Switch to less constipating opioid (e.g. fentanyl). (NICE)

• Switch to a combination of oxycodone hydrochloride with naloxone hydrochloride if the person's regular 24-hour opioid dose conversion is below maximum dose. (Consensus) expand arrow

The combination of oxycodone hydrochloride and naloxone hydrochloride has not been compared with laxatives in this patient population. (NPS Radar. Oxycodone-with-naloxone controlled-release tablets (Targin®). 2011(December) [cited 2012 20th October]; Available from: http://www.nps.org.au/__data/assets/pdf_file/0005/135869/oxycodone_with_naloxone.pdf)

• For patients receiving palliative care and for whom other laxative therapies are not indicated or effective, consider short-term use of methylnaltrexone. (NCCN, EAPC)


Warning! If opioid-induced hyperalgesia is suspected (e.g. pain is escalating despite pain management according to these guidelines), refer to consult a specialist pain medicine physician, palliative medicine physician palliative care team or palliative medicine specialist for urgent advice. ( Consensus).


Note Rule out other causes of constipation such as obstruction or hypercalcaemia

For more information on management of constipation and bowel obstruction, refer to recommendations and guidance of the Palliative Care Clinical Studies Collaborative.

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P21. When commencing an opioid and at each opioid dose increment, routinely prescribe 'as-required' prophylactic antiemetic (e.g. prochlorperazine maleate, metoclopramide or haloperidol). (EAPC, NCCN, NICE)
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P22. If nausea persists after symptom review, consider prescribing an antiemetic to be taken regularly. (ESMO, NCCN, NHS, NICE)
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P23. If nausea is persistent or severe, investigate further to determine causes (e.g. constipation, central nervous system pathology, chemotherapy, radiation therapy). (NCCN)


info
Recommended first-line anti-emetic agents
Haloperidol 0.5–1.5 mg orally twice per day
Metoclopramide hydrochloride 10–20 mg orally every 6-8 hours as needed
Prochlorperazine 5-10 mg orally every 6-8 hours as needed

Source: NCCN

For more information on management of emesis, refer to recommendations and guidance of the Palliative Care Clinical Studies Collaborative

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P24. If opioid toxicity is suspected (Consensus):

• Review all medicines and consider whether medicines may be contributing to the signs and symptoms.

• Take a detailed history and consider whether the person’s underlying disease (e.g. brain metastases, hepatic impairment) or other factors may be contributing to the signs and symptoms.

• Complete a thorough physical examination.

• Consider further investigations.


information Signs and symptoms of severe opioid toxicity

Sedation

Respiratory depression

Myoclonus

Pinpoint pupils

Seizures

Opioid-related toxicity of the central nervous system

Cognitive impairment

Confusion

Delirium

Hallucinations

Myoclonus

Sedation

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P25. When opioid-related toxicity of the central nervous system is suspected, consider the differential diagnosis of causes. Consider undertaking the following investigations as indicated by the clinical situation (Consensus):

• Ask about relevant history.

• Check electrolytes (sodium, potassium, chloride, serum calcium), urea, creatinine, calcium, glucose, liver function and oxygen saturations.

• Perform urine dipstick test.

• Order chest X-ray, CT of brain if indicated.

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P26. If opioid-related toxicity of the central nervous system is a probable cause of confusion or other central nervous system symptoms (NHS):

• Consider supplemental hydration if the patient is dehydrated.

• Consider switching to a different opioid or reducing dose and retitrate according to response.

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P27. For opioid-related confusion or delirium, treat the underlying aetiology and manage according to life expectancy (Consensus):

• If NOT last days of life, trial non-pharmacological management first to manage delirium symptoms (e.g. well lit, quiet environment). If the symptoms are not adequately improved consider reducing dose of opioid or switching to a different opioid.


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P28. Manage opioid-related myoclonus according to life expectancy (Consensus):

• Manage reversible causes such as renal impairment, dehydration, very high doses of opioids.

• If NOT last days of life, consider reducing dose of opioid or switching to a different opioid.

• If last days of life, consider reducing dose of opioid if appropriate and/or a benzodiazepine in addition to reducing opioid dose or switching opioid.

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P29. Respiratory depression is an uncommon adverse effect of opioid therapy for cancer pain.

If opioid-related respiratory depression is suspected (Consensus):

• Eliminate other causes such as effect of sedatives, hypercapnia and/or excessive oxygen flow.

• Check hydration status and renal function.

• For patients receiving methadone, consult a specialist pain medicine physician, palliative medicine physician, clinical pharmacist or clinical pharmacologist familiar with its use.

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P30. Manage opioid-related respiratory depression with all of the following (Consensus):

• Withhold opioid dose and recommence either at lower dosing frequency or reduced dose.

• Ensure the person is positioned properly.

• Rehydrate if dehydrated.

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P31. Manage opioid-related respiratory depression according to severity of symptom:

• Withhold next opioid dose and recommence either at a reduced dose or less frequent dosing interval.

• Ensure the person is positioned to maintain airway and provide oxygen if appropriate.

• If respiratory rate ≤ 8/minute and patient unrousable, use appropriate dose of naloxone in frequent small doses that aim to improve consciousness without worsening pain (diluting ampoule to 10mL). (ESMO, NCCN)

• If patient rousable (despite low respiratory rate), monitor patient closely for decrease in rousability until respiratory rate improves. Encourage deep breathing.

• For patients receiving fentanyl transdermal patches or methadone, consult a specialist pain medicine physician, palliative medicine physician, clinical pharmacist or clinical pharmacologist familiar with use of the agent.


Warning! In patients receiving methadone it may be difficult to investigate the cause of respiratory depression for because of the variable half-life of methadone (1–120 hours).

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P32. If opioid-related pruritis is suspected, exclude renal impairment and hepatic impairment as cause. (Consensus)
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P33. Manage opioid-related pruritis with either or both the following:

• Consider switching to a different opioid. (NCCN, NHS) If pruritis persists despite opioid switching after trialling more than one opioid, refer to a relevant specialist team (e.g. palliative care and/or pain medicine). (Consensus)

• Consider symptomatic management with an H1 antihistamine (choose one of the newer, less sedating agents). (Consensus)

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P34. Consider urinary retention in patients with urinary symptoms. (Consensus)
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P35. If opioid-induced hyperalgesia is suspected (e.g. pain is escalating despite pain management according to these guidelines), refer to palliative care team or palliative medicine specialist for urgent advice. (Consensus)


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Opioid rotation

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P36. Consider switching to a different opioid in either of the following situations:

• Optimal pain relief cannot be achieved despite appropriate dose. (ESMO, NCCN, NHS, NICE)

• The patient is experiencing unacceptable opioid-related adverse effects. (EAPC)

• If the oral route is no longer possible, switch to subcutaneous morphine, hydromorphone, oxycodone or fentanyl. Transdermal fentanyl is another alternative in stable pain. (NHS)

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P37. If switching to a different formulation or route of administration with the same agent, look up conversion for total 24-hour opioid dose via the eviQ Opioid Conversion Calculator. (EAPC, ESMO, NCCN, NHS, NICE)
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P38. If switching to a different agent because the previous route of administration is no longer possible, a starting dose lower than the equivalent total 24-hour opioid dose of the previous agent should be used. (EAPC)
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P39. If switching to a different opioid agent due to unacceptable treatment-related adverse effects, despite optimal pain relief, start with a lower dose, then adjust dose carefully while monitoring for pain control and adverse effects. (EAPC, ESMO)


Note Use the eviQ Opioid Conversion Calculator for calculating dose equivalence of transdermal fentanyl. Note that users need to set up a free account to access this tool

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Preventing misuse of opioids

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P40. If there is reason to suspect that a patient’s prescribed opioids are being misused or diverted:

• Explain to the person that goal is pain relief without misuse. (Consensus)

• Assess for opioid dependency disorder. (Consensus)

• Establish a treatment agreement with the person, including an agreement to limit the supply of opioids to a single prescriber and pharmacy. (NCCN)


information In Victoria, when opioids are suspected of being misused, it is a legal requirement that they be prescribed by a single prescriber and notification of the Department of Health, Drugs and Poisons Unit is mandatory.

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P41. Advise all patients and carers to ensure medicines are kept out of children’s reach, out of sight and in a secure cupboard. (Consensus)


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Assessing capacity to drive a vehicle

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P42. For patients taking opioids, assess capacity to drive using current national guidelines and warn of impairment at higher doses. (Consensus) expand arrow

Austroads Limited. Assessing fitness to drive. Medical standards for licensing and clinical management guidelines. Sydney: Austroads Ltd; 2012. Available from: http://www.austroads.com.au


information Cognitive performance is reduced early in treatment with opioids (mainly due to sedation) but the brain readily adapts. Therefore, a stable dose of opioid may not affect driving performance, provided the person is not taking other medicines that impair driving. (Austroads)

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Review and referral

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P43. If pain is not adequately controlled despite recommended pain management strategies, including analgesic medication, consult a specialist pain medicine physician or palliative medicine physician. (NICE, NHS)


Note If the prescribing clinician or other staff are unfamiliar with any agent under consideration, consult a specialist pain medicine physician, palliative medicine physician, clinical pharmacist or clinical pharmacologist who are familiar with the agent.


Note Refer for specialist review if:

• opioid-related adverse effects persist despite opioid switching after trialling more than one opioid

• opioid-induced hyperalgesia is suspected.

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References

Austroads Limited, Assessing fitness to drive. Medical standards for licensing and clinical management guidelines. 2012, Austroads Ltd: Sydney. Available from: http://www.austroads.com.au

Caraceni A, Hanks G, Kaasa S, European Palliative Care Research Collaborative. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations for the EAPC. Lancet Oncol 2012; 13: e58-e68. Web version available from: http://www.eapcnet.eu/LinkClick.aspx?fileticket=i-bB4cvZyzg%3d&tabid=1794

Davison SN, Koncicki H, Brennan F. Pain in Chronic Kidney disease- a Scoping review, Seminars in Dialysis 2014; 27: 188-204

National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Adult cancer pain. Version 2.2015: NCCN; 2015. Available from: http://www.nccn.org

National Health Service Quality Improvement Scotland. Best practice statement. The management of pain in patients with cancer. Edinburgh: NHS Quality Improvement Scotland; 2009. Available from: http://www.palliativecareguidelines.scot.nhs.uk/documents/PAINCANCERREV_BPS_NOV09.pdf

National Institute of Health and Care Excellence Guideline Development Group. Opioids in palliative care: safe and effective prescribing of strong opioids for pain in palliative care of adults. NICE clinical guideline 140. Manchester: NICE; 2012. Available from: http://www.nice.org.uk/nicemedia/live/13745/59285/59285.pdf

Porta-Sales J, Garzon-Rodriguez C, Llorens-Torrome S, Brunelli C, Pigni A, Caraceni A. Evidence on the analgesic role of bisphosphonates and denosumab in the treatment of pain due to bone metastases: A systematic review within the European Association for Palliative Care guidelines project. Palliat Med. 2016 Mar 22

Ripamonti CI, Bandieri E, Roila F, ESMO Guidelines Working Group. Management of cancer pain: ESMO clinical practice guidelines. Ann Oncol 2011; 22(Suppl 6): vi69-vi67. Available from: http://annonc.oxfordjournals.org/content/22/suppl_6/vi69.long

Scottish Intercollegiate Guidelines Network. Control of pain in adults with cancer. A national clinical guideline [Version amended 18 July 2011] Edinburgh: SIGN; 2008. Available from: http://www.sign.ac.uk/pdf/SIGN106.pdf

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