Pain in Palliative Care

Last updated 1 Jun 2026 · Palliative care

📋 Key Information Summary

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Pain affects 60–80% of patients with advanced cancer and up to 70% of those with other life-limiting illnesses in Australia; effective management is a core palliative care competency.
Use a systematic, validated pain assessment framework — the Edmonton Symptom Assessment System–Revised (ESAS-r) or a structured numerical rating scale (NRS) — at every clinical encounter and document the mechanism, severity, functional impact, and patient goals.
Distinguish nociceptive (somatic/visceral) from neuropathic pain, as the mechanism dictates pharmacological strategy: nociceptive pain responds to conventional analgesics, whereas neuropathic pain requires adjuvant agents (e.g. gabapentinoids, tricyclic antidepressants).
The WHO analgesic ladder (non-opioids → weak opioids → strong opioids) remains a useful framework but should be applied flexibly; patients with severe pain may require strong opioids from the outset.
Immediate-release (IR) oral morphine is the first-line strong opioid in most Australian palliative care settings (PBS-listed); start at 2.5–5 mg PO every 4 hours for opioid-naïve patients and titrate upward every 24–48 hours.
Regular reassessment of pain intensity, breakthrough analgesic use, and adverse effects must occur within 24–48 hours of any dose change; the breakthrough dose is typically 10–20% of the total daily opioid dose given every 2–4 hours as needed.
Opioid rotation (switching) is indicated for uncontrolled pain despite dose titration, intolerable adverse effects, or practical reasons (e.g. renal impairment, swallowing difficulties); equianalgesic dose conversions must be used with a 25–50% dose reduction.
Opioid-induced constipation (OIC) is almost universal and requires prophylactic laxatives (e.g. senna + macrogol) from opioid initiation; nausea typically self-resolves within 5 days but may require ondansetron or metoclopramide initially.
Adjuvant analgesics — corticosteroids (dexamethasone), gabapentinoids, low-dose ketamine, and nerve blocks — play a vital role in refractory pain and should be considered early when opioids alone are insufficient.
Aboriginal and Torres Strait Islander Australians access palliative care later, report higher pain scores, and face barriers including cultural disconnection, remote geography, and communication gaps; culturally safe, community-based approaches are essential.
Renal impairment (common in advanced illness) significantly alters opioid pharmacology — avoid morphine and codeine; fentanyl, hydromorphone, and buprenorphine are preferred.
Multidisciplinary involvement — specialist palliative care, pharmacy, physiotherapy, psychology, and allied health — improves pain outcomes and should be initiated early in the disease trajectory.

Introduction & Australian Epidemiology

Pain is among the most common and distressing symptoms experienced by adults and children with life-limiting illnesses. It impairs quality of life, functional capacity, psychological wellbeing, and dignity at the end of life. Effective pain management is a core domain of palliative care and is embedded within the National Palliative Care Standards (2018) and the NSQHS Standards for Comprehensive Care.

In Australia, approximately 170,000 people die each year, and an estimated 200,000 or more could benefit from palliative care annually. The AIHW reports that 60–80% of patients with advanced cancer experience moderate-to-severe pain, while pain prevalence among non-cancer palliative populations (heart failure, chronic obstructive pulmonary disease, end-stage kidney disease, motor neuron disease, dementia) ranges from 30–70%. Despite the availability of effective analgesic therapies, studies consistently show that 25–40% of Australian palliative care patients have inadequately managed pain at any given time.

Barriers to optimal pain management in Australia include clinician fears regarding opioids (addiction, regulatory scrutiny), inadequate training in pain assessment, delayed referral to specialist palliative care services, inequitable access in rural and remote areas, and unique cultural considerations for Aboriginal and Torres Strait Islander peoples. The Australian and New Zealand Society of Palliative Medicine (ANZSPM) and Palliative Care Australia advocate for earlier integration of palliative approaches, including pain management, alongside disease-modifying treatments.

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National context: The National Palliative Care Strategy 2018 and the End-of-Life Directions for Aged Care (ELDAC) project both mandate that all healthcare professionals, not just specialists, are competent in basic pain assessment and management for people with life-limiting conditions.

Pain Assessment

Comprehensive, individualised pain assessment is the foundation of effective palliative pain management. Assessment should be performed at every clinical encounter, using a structured framework, and documented in a standardised format. In palliative care, pain is understood as a multidimensional experience encompassing physical, psychological, social, and spiritual domains.

Assessment Framework: PQRST+ (Expanded)

A systematic approach to characterising pain enhances diagnostic accuracy and guides treatment selection.

Domain	Key Questions	Clinical Significance
P — Provocation / Palliation	What makes it worse? What relieves it?	Movement-related pain → consider bone metastasis or fracture; relief with position suggests musculoskeletal source
Q — Quality	Describe the pain: aching, burning, stabbing, tingling, cramping?	Burning, shooting, tingling → neuropathic component; aching, throbbing → nociceptive
R — Region / Radiation	Where exactly? Does it spread?	Dermatomal distribution → nerve compression; referred pain patterns (e.g. shoulder → diaphragm, liver capsule)
S — Severity	Numerical Rating Scale (NRS) 0–10 at rest and on movement	Mild (1–3), moderate (4–6), severe (7–10); assess worst, average, best in 24 hours
T — Timing	Constant vs intermittent? Worse at night?	Night pain suggesting bone metastasis; end-of-dose failure suggesting subtherapeutic dosing interval
+ — Functional / Psychosocial / Spiritual	How does pain affect sleep, mood, relationships, independence?	Pain is rarely purely physical — screen for distress, existential suffering, fear of death

Validated Assessment Tools

Tool	Population	Description
Numerical Rating Scale (NRS)	Adults who can self-report	0–10 scale; gold standard for verbal adults
ESAS-r	Adults with advanced illness	Validated 9-symptom tool (including pain); widely used in Australian palliative care services
Abbey Pain Scale	Patients with dementia who cannot self-report	Six domains assessed by observation; recommended by Dementia Support Australia
FLACC Scale	Children aged 2 months – 7 years	Face, Legs, Activity, Cry, Consolability; validated behavioural tool
PAINAD	Patients with dementia	Pain Assessment in Advanced Dementia; 5-item observational scale

Red Flags Requiring Urgent Evaluation

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Sudden onset severe back pain with neurological signs → suspected spinal cord compression (oncological emergency)
New-onset severe headache with vomiting, visual changes, or papilloedema → raised intracranial pressure
Severe bone pain with swelling after minimal trauma → pathological fracture
Acute abdomen in a patient on high-dose opioids → perforation, obstruction (opioids may mask peritonism)
Worsening pain despite dose escalation → reassess mechanism, consider nerve compression or new pathology

Ongoing Pain Assessment Principles

Reassess pain within 24–48 hours of any dose change or new intervention.
Document pain intensity at rest and on movement/walking.
Record breakthrough analgesic use (frequency, dose, response) as a surrogate marker of pain control.
Screen for psychological co-morbidity — anxiety and depression amplify pain perception; use the Distress Thermometer or PHQ-2.
In non-communicative patients, rely on behavioural cues (grimacing, guarding, agitation, moaning) using validated observational scales.
Assess patient's goals — some patients prioritise alertness over complete pain relief; patient-centred goal setting is essential.

Nociceptive vs Neuropathic Pain

Differentiating the pain mechanism is a critical step that directly influences pharmacological strategy. Many palliative care patients have mixed pain (both nociceptive and neuropathic components), requiring a multimodal approach.

Mechanism Comparison

Feature	Nociceptive Pain	Neuropathic Pain
Mechanism	Tissue damage activating peripheral nociceptors	Damage or dysfunction of somatosensory nervous system
Subtypes	Somatic: bone, muscle, connective tissue Visceral: organ capsule, peritoneum	Peripheral: nerve compression, chemotherapy-induced peripheral neuropathy (CIPN), post-herpetic neuralgia Central: cord compression, central post-stroke pain
Quality descriptors	Aching, throbbing, gnawing, sharp (somatic); deep, squeezing, cramping (visceral)	Burning, shooting, electric-shock, tingling, numbness, pins and needles
Dermatomal pattern	No (usually)	Often yes
Associated signs	Tenderness, swelling, guarding	Allodynia (pain to light touch), hyperalgesia, hypoesthesia
Common causes in palliative care	Bone metastases, liver capsule distension, bowel obstruction, soft-tissue infiltration, post-surgical	Brachial/lumbosacral plexopathy, cord compression, CIPN (vincristine, paclitaxel, oxaliplatin), post-herpetic neuralgia, phantom limb pain
First-line pharmacology	Paracetamol, NSAIDs, opioids	Gabapentinoids, TCAs, SNRIs; opioids as second-line

Bone Pain — A Special Case

Bone metastases are the most common cause of pain in advanced cancer. The mechanism is both nociceptive (periosteal stretching, microfractures) and neuropathic (nerve infiltration by tumour). Management combines:

Analgesics: Opioids ± paracetamol ± NSAIDs (monitor renal function, GI risk).
Corticosteroids: Dexamethasone 4–8 mg daily (reduces peri-tumoural oedema).
Bone-modifying agents: Denosumab (Xgeva®) 120 mg SC every 4 weeks or zoledronic acid 4 mg IV every 4 weeks — PBS-listed for bone metastases from solid tumours.
Palliative radiotherapy: Single-fraction (8 Gy) or multi-fraction regimens; effective in 60–80% of cases — refer to radiation oncology.
Interventional procedures: Cementoplasty for acetabular/vertebral metastases; radiofrequency ablation for oligometastatic painful bone lesions.

Neuropathic Pain — Diagnostic Criteria

The IASP grading system for probable neuropathic pain requires:

Pain with a plausible neuroanatomical distribution.
History of a relevant lesion or disease of the somatosensory nervous system.
At least one confirmatory test (e.g. nerve conduction studies, MRI showing nerve root compression, clinical signs of allodynia/hyperalgesia in a dermatomal distribution).

In the palliative setting, formal neurophysiological testing may be impractical; clinical assessment is usually sufficient to initiate neuropathic analgesic therapy.

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Mixed pain is common: Up to 40% of cancer pain has both nociceptive and neuropathic components. Failure to recognise the neuropathic element is a leading cause of opioid-resistant pain. Systematically ask about burning, tingling, electric-shock sensations, and allodynia.

Opioids

Opioids are the mainstay of moderate-to-severe pain management in palliative care. In Australia, immediate-release oral morphine is the most accessible first-line strong opioid, supported by decades of clinical experience, robust PBS listing, and familiar management of adverse effects. The choice of opioid, dose, route, and formulation should be individualised based on pain severity, mechanism, renal and hepatic function, swallowing capacity, patient preference, and prior opioid exposure.

Opioid Initiation — Opioid-Naïve Patients

Assess & Confirm Indication

Moderate-to-severe pain (NRS ≥ 4/10) not controlled by non-opioid agents. Ensure pain mechanism has been characterised. Check renal function (eGFR), hepatic function, and current medications.

Start Low, Titrate

Morphine IR 2.5–5 mg PO every 4 hours (elderly/renally impaired: 1.5–2.5 mg). Provide a breakthrough dose (10–20% of total daily dose) every 2 hours PRN. Titrate upward every 24–48 hours based on response and breakthrough use.

Prevent & Manage Adverse Effects

Commence prophylactic laxatives (senna + macrogol) from day one. Prescribe PRN anti-emetic (metoclopramide 10 mg PO TDS or haloperidol 0.5–1 mg PO nocte) — nausea usually resolves within 5 days. Counsel re drowsiness (usually transient, 2–5 days).

Convert to Modified-Release (if appropriate)

Once stable 24-hour dose is established, convert to modified-release (MR) morphine (e.g. MS Contin®, Kapanol®) given every 12 hours. Retain IR morphine for breakthrough. Round to nearest practical dose.

Strong Opioid Options — Australian Context

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Morphine (IR & MR)

MS Contin® · Kapanol® · Sevredol® · Ordine® · Opioid analgesic

Adult dose (opioid-naïve) IR: 2.5–5 mg PO every 4 hours; titrate every 24–48 h. MR: 10–20 mg PO every 12 h (converted from stable total daily IR dose)

Paediatric dose IR: 0.2–0.4 mg/kg PO every 4 hours (max initial 5 mg); specialist guidance recommended

Breakthrough dose 10–20% of total daily dose every 2–4 hours PRN (IR formulation)

Renal adjustment AVOID if eGFR < 30 mL/min — active metabolites (M6G, M3G) accumulate → neurotoxicity, myoclonus, respiratory depression. Switch to fentanyl or hydromorphone.

Hepatic adjustment Reduce dose by 50% in severe hepatic impairment; avoid in acute liver failure

PBS status ✔ PBS General Benefit (IR and MR formulations)

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Oxycodone (IR & MR)

OxyNorm® · Endone® · OxyContin® · Opioid analgesic

Adult dose (opioid-naïve) IR: 2.5–5 mg PO every 4–6 hours. MR (OxyContin®): 5–10 mg PO every 12 hours

Equianalgesic ratio Oral oxycodone : oral morphine ≈ 1 : 1.5 (i.e. 10 mg oxycodone ≈ 15 mg morphine)

Renal adjustment Use with caution if eGFR < 30 mL/min; reduced clearance. Consider dose reduction 50%.

Hepatic adjustment Reduce dose in moderate–severe hepatic impairment; start low, titrate slowly

PBS status ✔ PBS General Benefit

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Fentanyl (transdermal patch)

Durogesic DTrans® · Generic · Opioid analgesic

Adult dose Apply patch to non-irradiated, non-oedematous skin every 72 hours. Starting dose: 12 mcg/h (for patients already on stable opioid equivalent of ~30–60 mg oral morphine/day). Use IR opioid for breakthrough.

Key notes NOT for opioid-naïve patients. Slow onset (12–24 h to steady state). Avoid in rapidly changing pain, febrile patients (↑ absorption), or cachectic patients with poor subcutaneous tissue. Remove before MRI/radiotherapy.

Renal adjustment PREFERRED in renal impairment — no active renally-cleared metabolites. Safe in eGFR < 30 and dialysis.

PBS status ✔ PBS General Benefit

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Hydromorphone

Jurnista® (MR) · Dilaudid® (IR) · Opioid analgesic

Adult dose (opioid-naïve) IR: 0.5–1 mg PO every 4 hours. MR (Jurnista®): 2 mg PO every 24 hours. Also available as SC infusion (0.5–1 mg/h).

Equianalgesic ratio Oral hydromorphone : oral morphine ≈ 1 : 5 (i.e. 1.3 mg hydromorphone ≈ 5 mg morphine)

Renal adjustment PREFERRED in moderate–severe renal impairment (eGFR < 30) — safer metabolite profile than morphine. Start at 50% dose reduction.

PBS status ⚠ PBS Authority Required (Jurnista® — Authority for chronic severe pain)

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Buprenorphine (transdermal)

Norspan® · Opioid partial agonist

Adult dose 5 mcg/h patch every 7 days (opioid-naïve). Titrate to 10, 20 mcg/h as needed. Suited to stable, moderate pain.

Renal adjustment Safe in renal impairment — no dose adjustment required

Key notes May precipitate withdrawal if switching from a full agonist to buprenorphine — consult specialist palliative care. Ceiling effect for respiratory depression (safety advantage).

PBS status ✔ PBS General Benefit

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Methadone

Physeptone® · Opioid agonist

Role Reserved for refractory pain where other opioids have failed. Has NMDA receptor antagonist activity (useful in neuropathic/opioid-resistant pain). Long and variable half-life (15–60 h).

Adult dose Initiate 2.5–5 mg PO every 8–12 hours with close monitoring. Titrate cautiously after 5–7 days due to accumulation. Variable equianalgesic ratios — must involve specialist pain/palliative care.

Key notes Risk of QTc prolongation — baseline and follow-up ECGs required. Drug interactions with CYP3A4/2B6 inhibitors/inducers. Requires experienced prescriber.

PBS status ⚠ PBS Authority Required

Weak Opioids

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Tramadol

Tramal® · Tramahexal® · Weak opioid + SNRI

Adult dose 50–100 mg PO every 4–6 hours; max 400 mg/day. MR: 100–200 mg every 12 hours.

Renal adjustment Max 200 mg/day if eGFR < 30 mL/min; avoid if eGFR < 15

Key notes Lower efficacy ceiling than strong opioids. Risk of serotonin syndrome with SSRIs/SNRIs/MAOIs. Seizure risk. Generally regarded as having limited role in palliative care — most patients benefit from direct titration of low-dose strong opioids.

PBS status ✔ PBS General Benefit

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Codeine

Panadeine Forte® (combined with paracetamol) · Weak opioid prodrug

Adult dose 30–60 mg PO every 4–6 hours (as codeine phosphate). Often used as fixed-dose combination with paracetamol 500 mg.

Key notes Prodrug — requires CYP2D6 metabolism. Ultra-rapid metabolisers at risk of toxicity; poor metabolisers get no analgesia. Avoid in renal impairment. Limited role in palliative care compared with low-dose morphine.

PBS status ✔ PBS General Benefit

Opioid Dose Equivalence Guide (Approximate)

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Safety note: Equianalgesic tables are guides only. When rotating opioids, reduce the calculated equianalgesic dose by 25–50% (cross-tolerance is incomplete) and titrate to effect. Individual variability is significant. Always consult a pharmacist or specialist palliative care service when converting.

Opioid	Approximate equianalgesic dose (relative to 30 mg oral morphine/24 h)	Onset (oral)	Duration
Oral morphine	30 mg	30 min (IR)	4 h (IR) / 12 h (MR)
Oral oxycodone	~20 mg	20–30 min (IR)	4–6 h (IR) / 12 h (MR)
Oral hydromorphone	~6 mg	30 min	4 h (IR) / 24 h (MR – Jurnista®)
Transdermal fentanyl (patch)	12 mcg/h ≈ 30–60 mg oral morphine/day	12–24 h	72 h
Transdermal buprenorphine	5 mcg/h ≈ ~12 mg oral morphine/day	12–24 h	168 h (7 days)

Managing Opioid Adverse Effects

Adverse Effect	Incidence	Management
Constipation	~95% (does not develop tolerance)	Prophylactic senna 1–2 tabs nocte + macrogol 3350 1–2 sachets daily. If refractory: lactulose, rectal interventions. Peripherally-acting mu-opioid receptor antagonists (PAMORAs — naloxegol, methylnaltrexone) for refractory OIC — specialist initiation.
Nausea	~30% (usually resolves in 5 days)	Metoclopramide 10 mg PO/SC TDS PRN or haloperidol 0.5–1 mg PO nocte. Avoid metoclopramide in bowel obstruction → use ondansetron 4–8 mg PO/IV or cyclizine 50 mg PO/SC TDS.
Drowsiness / Sedation	~20% (often transient, 2–5 days)	Usually self-resolving. If persistent → reduce dose, rotate opioid, or add dexamethasone 4 mg daily or methylphenidate 2.5–5 mg mane (specialist use).
Delirium / Confusion	Variable	Rule out other causes (sepsis, metabolic, medications). Reduce dose or rotate opioid. Haloperidol 0.5–1.5 mg PO/SC for agitation. Consider midazolam for refractory terminal delirium.
Myoclonus	~5–10% (dose-related)	Reduce dose, rotate opioid. Clonazepam 0.5–1 mg PO/SC or midazolam SC if distressing. Check renal function — morphine metabolites accumulate.
Respiratory depression	Rare with proper titration	Naloxone 0.04–0.4 mg IV/SC (diluted, titrated to effect). In palliative care, use very low doses to reverse toxicity without precipitating acute withdrawal or uncontrolled pain.

Alternative Routes of Administration

When the oral route is unavailable (dysphagia, vomiting, reduced consciousness, bowel obstruction):

Subcutaneous (SC) continuous infusion via syringe driver (e.g. CADD-MS 3 or Niki T34) — most common alternative route in Australian palliative care. Use opioid at 50–66% of the oral dose in equianalgesic conversion.
Transdermal fentanyl or buprenorphine patches — suitable for stable pain; not for rapidly titrating or breakthrough.
Sublingual fentanyl (Abstral®, Actiq®, Instanyl®) — rapid-onset for breakthrough pain in patients unable to swallow; PBS-listed (Authority Required).
Rectal — morphine suppositories available but rarely used in practice.
Transmucosal routes — intranasal fentanyl (Instanyl®) or buccal formulations for rapid breakthrough pain control.

Opioid Rotation (Switching)

Indications for opioid rotation include:

Uncontrolled pain despite adequate dose titration (i.e. dose-limiting toxicity before analgesic efficacy).
Intolerable or unmanageable adverse effects (e.g. morphine-induced neurotoxicity in renal impairment).
Practical considerations (e.g. swallowing difficulty necessitating patch, renal deterioration).

Method: Calculate the total 24-hour dose of the current opioid → convert to equianalgesic dose of the new opioid → reduce by 25–50% (incomplete cross-tolerance) → provide breakthrough doses of the new opioid → reassess in 24–48 hours.

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Methadone conversion warning: Equianalgesic ratios for methadone are highly variable and depend on the current opioid dose (higher doses → greater relative potency of methadone). Conversions to/from methadone should only be performed by or in consultation with an experienced palliative care physician or pharmacist. ECG monitoring for QTc prolongation is mandatory.

Adjuvant Analgesics

Adjuvant analgesics are medications whose primary indication is not pain but that have demonstrated analgesic efficacy in specific pain contexts. They are essential in multimodal pain management, particularly for neuropathic pain, bone pain, raised intracranial pressure, and visceral distension. They may be used alone for mild pain or — more commonly — combined with opioids for moderate-to-severe or refractory pain.

Non-Opioid Analgesics

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Paracetamol

Panadol® · Panamax® · Non-opioid analgesic

Adult dose 500 mg–1 g PO every 4–6 hours; max 4 g/day (2 g/day if weight < 50 kg or hepatic impairment)

Paediatric dose 15 mg/kg PO every 4–6 hours; max 60 mg/kg/day

Renal adjustment Generally safe; no specific dose reduction required. Use with caution in severe renal impairment.

Key notes Useful adjunct; limited evidence as sole analgesic in moderate-severe cancer pain. IV paracetamol available for patients unable to take oral medications.

PBS status ✔ PBS General Benefit (also available OTC)

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Ibuprofen

Nurofen® · Brufen® · NSAID

Adult dose 200–400 mg PO every 6–8 hours; max 1.2 g/day (OTC) or 2.4 g/day (prescription)

Key notes Effective for bone pain and soft-tissue inflammation. Use lowest effective dose for shortest duration. Co-prescribe PPI (e.g. omeprazole 20 mg daily) for GI protection. Avoid if eGFR < 30 mL/min, active GI bleeding, or severe heart failure.

PBS status ✔ PBS General Benefit

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Celecoxib

Celebrex® · Selective COX-2 inhibitor NSAID

Adult dose 100–200 mg PO once or twice daily

Key notes Lower GI bleeding risk than non-selective NSAIDs but still requires caution. Cardiovascular risk — avoid in significant ischaemic heart disease. No renal advantage over non-selective NSAIDs.

PBS status ⚠ PBS Authority Required

Corticosteroids

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Dexamethasone

Dexamethasone® · Dexsol® · Corticosteroid

Indications in palliative pain Bone pain (peri-tumoural oedema), spinal cord compression, raised ICP (brain metastases), nerve compression/plexopathy, visceral capsular distension (hepatic metastases), bowel obstruction (anti-inflammatory)

Adult dose 4–8 mg PO/IV once daily (morning); higher loading doses (8–16 mg) for cord compression or raised ICP. Taper to lowest effective dose over 1–2 weeks once benefit achieved.

Key notes Avoid long-term use without review (myopathy, hyperglycaemia, immunosuppression, insomnia). Prophylaxis against gastric irritation (PPI). Monitor BSL in diabetics. Morning dosing preferred to reduce insomnia.

PBS status ✔ PBS General Benefit

Neuropathic Pain Adjuvants

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Gabapentin

Neurontin® · Gabahexal® · Anticonvulsant / gabapentinoid

Adult dose Start 100–300 mg PO at night, titrate by 100–300 mg every 3–5 days. Target dose: 300–600 mg TDS (max 3.6 g/day, though often effective at lower doses in palliative care).

Renal adjustment Dose reduction required: eGFR 30–59: max 600–1200 mg/day; eGFR 15–29: max 300–600 mg/day; eGFR < 15: max 150–300 mg/day or avoid

Key notes Effective for CIPN, post-herpetic neuralgia, and neuropathic pain of various causes. Slow titration to minimise drowsiness and dizziness. Sudden withdrawal can cause seizures — taper over ≥ 7 days.

PBS status ⚠ PBS Authority Required

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Pregabalin

Lyrica® · Gabapentinoid

Adult dose Start 25–75 mg PO twice daily; titrate every 3–7 days. Target dose: 75–150 mg BD (max 300 mg BD). Faster onset than gabapentin.

Renal adjustment eGFR 30–59: max 300 mg/day in divided doses; eGFR 15–29: max 150 mg/day; eGFR < 15: max 75 mg/day or avoid

Key notes Useful for CIPN, post-herpetic neuralgia, and generalised neuropathic pain. May cause peripheral oedema, weight gain, sedation. Potential for misuse — S8 in some Australian states.

PBS status ⚠ PBS Authority Required

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Amitriptyline

Endep® · Triptafen® · Tricyclic antidepressant (TCA)

Adult dose (analgesic) Start 5–10 mg PO at night; titrate every 5–7 days. Analgesic dose: 25–75 mg nocte (lower than antidepressant dose). Allow 2–4 weeks for full effect.

Key notes Evidence for neuropathic pain (post-herpetic neuralgia, CIPN). Anti-cholinergic adverse effects (dry mouth, constipation, urinary retention, cardiac conduction delay). Avoid in significant cardiac disease (check ECG). Caution in elderly — risk of falls, confusion.

PBS status ✔ PBS General Benefit

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Duloxetine

Cymbalta® · SNRI antidepressant

Adult dose Start 30 mg PO daily for 1 week, then increase to 60 mg daily. Max 120 mg/day.

Key notes NICE-recommended first-line for neuropathic pain. Evidence in diabetic peripheral neuropathy and CIPN. Avoid in severe hepatic impairment. May cause nausea (transient), dry mouth, constipation. Discontinuation syndrome — taper gradually.

PBS status ⚠ PBS Authority Required

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Lidocaine 5% medicated plasters

Versatis® · Local anaesthetic

Adult dose Apply up to 3 plasters to affected area for 12 hours on / 12 hours off. Cover only intact, non-irradiated skin.

Key notes Evidence for post-herpetic neuralgia and localised neuropathic pain. Minimal systemic absorption. Useful in elderly or patients unable to tolerate systemic agents. Can be cut to size.

PBS status ✘ Not PBS-listed (significant out-of-pocket cost)

Specialist / Refractory Pain Agents

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Ketamine (sub-anaesthetic doses)

Ketalar® · NMDA receptor antagonist

Role Used in refractory pain, particularly opioid-resistant neuropathic pain and complex regional pain. NMDA receptor antagonism may reduce opioid tolerance and central sensitisation.

Dose (specialist-initiated) SC or IV: 0.1–0.3 mg/kg/h as continuous infusion (start low, titrate). Some protocols use 0.1–0.5 mg/kg SC/IV every 4–6 hours. Oral/sublingual: 0.25–0.5 mg/kg TDS (limited bioavailability). Duration: typically 3–5 day course.

Key notes Requires specialist palliative care supervision. Monitor for dissociative effects, hallucinations, nausea, hypertension. Co-prescribe midazolam 1–2 mg PRN for dysphoria. Not for routine use.

PBS status ✔ PBS General Benefit (S4 — hospital/specialist use common)

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Clonazepam (sublingual)

Rivotril® · Benzodiazepine

Adult dose 0.5 mg sublingual BD; titrate to 1–2 mg BD. Useful for myoclonus, anxiety-related pain, and as co-analgesic.

Key notes Anticonvulsant and muscle relaxant properties. Can assist with co-existent anxiety. Sedation, respiratory depression risk when combined with opioids — use cautiously in frail or elderly patients.

PBS status ✔ PBS General Benefit

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Bisphosphonates / Denosumab

Zometa® (zoledronic acid) · Xgeva® (denosumab) · Bone-modifying agents

Zoledronic acid 4 mg IV over ≥ 15 minutes every 4 weeks. Monitor renal function. Correct hypocalcaemia and vitamin D deficiency before initiation.

Denosumab 120 mg SC every 4 weeks. Can be used in renal impairment (unlike bisphosphonates). Monitor calcium — risk of hypocalcaemia. ONJ risk — dental review before initiation.

Key notes Reduce skeletal-related events (fracture, cord compression, need for radiotherapy) in bone metastases from solid tumours and multiple myeloma. Analgesic effect builds over 2–4 weeks. Not a substitute for analgesics in acute pain.

PBS status ⚠ PBS Authority Required

Interventional Approaches (Specialist)

When pharmacological therapy is insufficient or dose-limited due to adverse effects, interventional strategies may provide significant benefit:

Nerve blocks: Coeliac plexus block (visceral pain from pancreatic/upper GI tumours), superior hypogastric plexus block (pelvic pain), intercostal nerve blocks — image-guided by pain medicine specialist or interventional radiologist.
Neuraxial (epidural/intrathecal) analgesia: For refractory pain below T6; catheter-delivered local anaesthetic ± opioid ± clonidine. Requires specialist pain/palliative care service and ongoing monitoring.
Palliative radiotherapy: Single-fraction 8 Gy for painful bone metastases (widely available across Australian radiation oncology centres). Also for cord compression, brain metastases.
Cementoplasty / radiofrequency ablation: For painful pelvic, acetabular, or vertebral metastases. Available at major tertiary centres.
Intrathecal baclofen pump: For refractory spasticity-related pain (specialist indication).

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Non-pharmacological strategies should always complement pharmacotherapy: physiotherapy (gentle mobilisation, positioning), TENS (transcutaneous electrical nerve stimulation), heat/cold packs, massage, relaxation and mindfulness techniques, psychological support (cognitive-behavioural therapy for pain), and occupational therapy. Refer to allied health early in the pain management plan.

Special Populations

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Renal Impairment

Key concern: Morphine and codeine produce active renally-cleared metabolites (M6G, M3G, morphine-6-glucuronide) that accumulate when eGFR < 30 mL/min, causing prolonged sedation, myoclonus, respiratory depression, and seizures.

Preferred opioids:

Fentanyl (transdermal or SC) — safest in renal failure, including dialysis
Hydromorphone — safer metabolite profile; start at 50% dose reduction if eGFR < 30
Buprenorphine (transdermal) — no dose adjustment required

Avoid: Morphine, codeine, tramadol (all have active renally-cleared metabolites). Gabapentinoids require significant dose reduction — see individual drug renal dosing above.

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Hepatic Impairment

Key concern: Reduced hepatic metabolism prolongs opioid half-life and increases bioavailability of oral opioids (reduced first-pass effect).

Principles:

Reduce all opioid doses by 25–50% in moderate–severe hepatic impairment (Child-Pugh B or C)
Fentanyl may be used cautiously — metabolised hepatically but no active metabolites
Avoid tramadol (seizure risk, serotonin syndrome) and codeine (reduced efficacy)
Paracetamol: limit to 2 g/day in chronic liver disease
NSAIDs: avoid if possible (coagulopathy, renal risk, GI bleeding)
Dexamethasone: use with caution — may precipitate encephalopathy in advanced liver disease

Monitor: LFTs, coagulation, albumin. Low albumin increases free fraction of highly protein-bound drugs.

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Elderly (≥ 65 years)

Key concerns: Altered pharmacokinetics (reduced renal clearance, increased fat distribution, reduced albumin), polypharmacy, frailty, falls risk, cognitive impairment.

Principles:

Start opioids at 50% of standard adult dose; titrate more slowly (every 48–72 h)
Prefer shorter-acting agents initially to gauge response
Use the Abbey Pain Scale or PAINAD for patients with dementia who cannot self-report
Monitor closely for delirium, sedation, constipation, urinary retention, falls
Avoid TCAs if possible (anticholinergic burden); prefer gabapentinoids at lower doses
Ensure home medication review to reduce polypharmacy interactions

ELDAC toolkit: End-of-Life Directions for Aged Care provides guidance on pain assessment and management in residential aged care facilities.

👶

Paediatrics

Key concerns: Developmentally appropriate assessment, weight-based dosing, fear of procedures, communication barriers.

Principles:

Use validated age-appropriate pain scales: FLACC (2 months–7 years), Wong-Baker FACES (3–18 years), NRS (≥ 8 years)
Paracetamol: 15 mg/kg PO every 4–6 hours (max 60 mg/kg/day)
Ibuprofen: 5–10 mg/kg PO every 6–8 hours
Morphine IR: 0.2–0.4 mg/kg PO every 4 hours; titrate cautiously. SC: 0.1–0.2 mg/kg every 4 hours.
Gabapentin: 5–10 mg/kg/day in 2–3 divided doses; titrate to 25–35 mg/kg/day (max 3.6 g/day)

Referral: Paediatric palliative care services (e.g. Bear Cottage, Very Special Kids, state-based services) should be involved early. Multidisciplinary approach with play therapists, child psychologists, and family support workers.

🤰

Pregnancy & Breastfeeding

Context: Palliative care in pregnancy is rare but occurs in advanced cancer, motor neuron disease, and other life-limiting conditions.

Principles:

Paracetamol is safe in all trimesters
Opioids: codeine and morphine are Category A (TGA). However, late pregnancy use can cause neonatal respiratory depression and withdrawal — neonatology team should be involved
Avoid NSAIDs in the third trimester (risk of premature ductus arteriosus closure, oligohydramnios)
Gabapentinoids: limited safety data — generally avoided unless benefits outweigh risks; discuss with maternal-fetal medicine
Consult with maternal-fetal medicine and palliative care teams concurrently

🛡️

Immunocompromised Patients

Context: Includes patients on chemotherapy, post-transplant, HIV/AIDS, and those on long-term corticosteroids.

Principles:

Infection can present as new or worsening pain — maintain a low threshold for infection screening (especially in neutropenic patients)
NSAIDs: use cautiously in thrombocytopenia (bleeding risk) and renal impairment (common post-transplant)
Corticosteroids: may mask infection; monitor for hyperglycaemia in post-transplant patients on tacrolimus/steroids
CIPN is common — assess mechanism carefully before escalating opioids (neuropathic adjuvants may be more effective)

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Australians experience a significantly higher burden of life-limiting illness and cancer, yet access palliative care services later and less frequently than non-Indigenous Australians. Pain management in this population must account for historical, cultural, geographical, and systemic factors that influence health outcomes.

Late presentation and delayed referral

Aboriginal and Torres Strait Islander people are more likely to present with advanced disease and experience higher symptom burden at diagnosis. Contributing factors include delayed help-seeking, diagnostic delays, and under-referral to specialist palliative care. Culturally safe early referral pathways must be established.

Geographic and service access barriers

Many Aboriginal and Torres Strait Islander people live in rural and remote communities where specialist palliative care services, pain medicine specialists, and pharmacies are scarce or absent. Telehealth, visiting specialist services, and community-controlled health organisations (ACCHOs) play a critical role. PBS Section 100 (Remote Area Aboriginal Health Services) supplies medicines to these communities.

Cultural understandings of pain and dying

Pain and illness may be understood through cultural and spiritual frameworks that differ from Western biomedical models. Some patients may not verbalise pain in numerical terms or may express pain through storytelling and metaphor. Open, non-judgmental, and culturally humble conversations are essential. Avoid assumptions — ask the patient and family how they understand and wish to manage pain.

Stigma around opioids and "sorry business"

Fear of opioid addiction, historical mistrust of government health systems, and concerns about medication side effects may lead to opioid refusal or non-adherence. Provide clear, respectful education about opioid use for pain in palliative care. Involve family and community in shared decision-making. "Sorry business" (mourning practices) may require flexibility in treatment schedules and community-based care.

Language and health literacy

English may be a second, third, or fourth language for many patients. Health literacy levels vary. Use plain language, visual aids, and Aboriginal health workers or interpreters (including Aboriginal Interpreter Services in the NT and WA) to explain pain assessment tools and medication use. Written information should be culturally and linguistically appropriate.

Preference for dying on Country

Many Aboriginal and Torres Strait Islander people express a strong preference to return to their Country (traditional lands) to die. This requires community-based palliative care models, GP-led shared care, adequate supply of medications (including syringe drivers and subcutaneous infusions), and coordination between metropolitan hospitals, ACCHOs, and remote health clinics. The National Aboriginal Community Controlled Health Organisation (NACCHO) supports integrated palliative care within primary healthcare.

ℹ️

Practical strategies: Partner with local Aboriginal health workers and liaison officers. Use tools such as the "Pain Puzzle" (developed for culturally and linguistically diverse groups). Ensure opioid prescriptions are communicated clearly to remote pharmacies and clinic staff. Support community-controlled models of end-of-life care. Refer early to state/territory palliative care services with Aboriginal health programs (e.g. SA Palliative Care Aboriginal Health Program, NT Palliative Care).

📚 References

1. World Health Organization. WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. Geneva: WHO; 2018.
2. Palliative Care Australia. National Palliative Care Standards. 5th ed. Canberra: Palliative Care Australia; 2018.
3. Australian Institute of Health and Welfare. Palliative care services in Australia. Cat. no. HWV 82. Canberra: AIHW; 2023.
4. Fallon M, Giusti R, Aielli F, et al. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29(Suppl 4):iv166–iv191.
5. Caraceni A, Hanks G, Kaasa S, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol. 2012;13(2):e58–e68.
6. Australian and New Zealand Society of Palliative Medicine (ANZSPM). Position Statement: Opioid Use in Palliative Medicine. Sydney: ANZSPM; 2020.
7. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162–173.
8. National Health and Medical Research Council (NHMRC). Clinical Practice Guidelines for the Management of Mesothelioma and Palliative Care Principles for Lung Cancer. Canberra: NHMRC; 2020.
9. Duggleby W, Thompson SA, Baxter A, et al. Aboriginal and Torres Strait Islander peoples' experiences of palliative care: a systematic review. Aust J Prim Health. 2021;27(5):355–366.
10. Royal Australian College of General Practitioners (RACGP). Specific Interests Palliative Care Network: A Guide for GPs Managing Pain at End of Life. Melbourne: RACGP; 2021.
11. Cherny NI, Fallon MT, Kaasa S, et al., eds. Oxford Textbook of Palliative Medicine. 5th ed. Oxford: Oxford University Press; 2015.
12. Palliative Care Australia. National Consensus Statement: Essential Elements for Safe and High-Quality End-of-Life Care. Sydney: Australian Commission on Safety and Quality in Health Care; 2015.
13. Currow DC, Allingham S, Yates P, et al. Improving national hospice/palliative care service symptom outcomes measured through the Palliative Care Outcomes Collaboration (PCOC). Med J Aust. 2015;202(4):195–199.
14. McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. Cochrane Database Syst Rev. 2013;(8):CD006146.
15. National Aboriginal Community Controlled Health Organisation (NACCHO). Providing Palliative Care for Aboriginal and Torres Strait Islander Peoples: A Practice Guide. Canberra: NACCHO; 2019.

for PBS scripts. Utilise ACCHS pharmacies and Remote Area Aboriginal Health Worker programs for medication supply in remote areas. Avoid initiating benzodiazepines; support holistic pain management including community-based exercise programs.

Preventive health

Promote bone health: encourage vitamin D supplementation (1000 IU daily in deficient individuals), smoking cessation support, reduction of alcohol intake, and weight-bearing exercise. MBS Item 715 health checks provide a structured opportunity to assess bone health, screen for osteoporosis risk factors, and discuss musculoskeletal health in a culturally safe context.

Quick Reference: Differential Diagnosis at a Glance

Costovertebral dysfunction

Paracetamol ± NSAID; manual therapy

2–6 weeks

Provocable on palpation; no red flags

Thoracic compression fracture

Paracetamol; ± calcitonin; DXA + osteoporosis Rx

6–12 weeks healing

Elderly; osteoporosis; acute onset

ACS (posterior MI)

Aspirin 300 mg, GTN, heparin; urgent PCI

Time-critical

ECG, troponin; CV risk factors

Aortic dissection

IV labetalol; urgent CT aortogram; surgery (Type A)

Time-critical

Tearing pain; BP differential >20 mmHg

Vertebral osteomyelitis

IV antibiotics (vancomycin + ceftriaxone initially); ID consult

6 weeks IV antibiotics

Fever, elevated CRP, IV drug use

Biliary colic / cholecystitis

Paracetamol ± morphine; lap cholecystectomy

Surgical within 72 h (cholecystitis)

RUQ/infrascapular; post-prandial; RUQ US

📚 References

1. Briggs AM, Smith AJ, Straker LM, Bragge P. Thoracic spine pain in the general population: prevalence, incidence and associated factors in children, adolescents and adults. A systematic review. BMC Musculoskelet Disord. 2009;10:77.
2. National Health and Medical Research Council (NHMRC). Evidence-based management of acute musculoskeletal pain. Canberra: NHMRC; 2003 (updated 2020).
3. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander Health Performance Framework: Summary report 2023. Canberra: AIHW; 2023.
4. Deyo RA, Rainville J, Kent DL. What can the history and physical examination tell us about low back pain? JAMA. 1992;268(6):760–765.
5. Stochkendahl MJ, Kjaer P, Hartvigsen J, et al. National Clinical Guidelines for non-surgical treatment of patients with recent onset low back pain or lumbar radiculopathy. Europ Spine J. 2018;27(1):60–75.
6. Erwin WM, Jackson PC, Homonko DA. Innervation of the human costovertebral joint: implications for clinical back pain syndromes. J Manipulative Physiol Ther. 2000;23(6):395–403.
7. Royal Australian College of General Practitioners (RACGP). Guidelines for preventive activities in general practice. 9th edn. Melbourne: RACGP; 2018 (updated 2023).
8. Hirsch JA, Singh V, Falco FJE, et al. Thoracic facet joint interventions. Pain Physician. 2016;19(4):E581–E593.
9. Erwin WM, Jackson PC. The costovertebral joint: anatomy, biomechanics, and clinical significance in thoracic back pain syndromes. J Can Chiropr Assoc. 2003;47(2):112–120.
10. Strayer RJ, Gunnerson JM, Brown LH, et al. Aortic dissection: clinical features, diagnosis, and management. Aust Crit Care. 2019;32(2):144–153.
11. Ombregt L. A system of orthopaedic medicine. 3rd edn. Edinburgh: Churchill Livingstone Elsevier; 2013. Chapter 18: Thoracic spine.
12. Lin CC, Chen KH, Li DM, et al. Characteristics and outcomes of patients presenting with thoracic back pain to the emergency department. Emerg Med Australas. 2020;32(5):805–811.

for PBS-listed medicines at participating pharmacies.

Cultural safety

Engagement with Aboriginal Community Controlled Health Organisations (ACCHOs) is essential. Cultural safety training for non-Indigenous clinicians, use of Aboriginal Health Workers and Liaison Officers, and incorporation of traditional healing practices alongside Western medicine improve treatment adherence and outcomes. Avoidance of eye contact, respect for gender-sensitive examination practices, and understanding of sorry business protocols are critical elements of culturally safe care.

Medication adherence

Complex DMARD regimens with frequent monitoring requirements present adherence challenges. Long-acting depot injections (e.g., methotrexate SC) may improve adherence compared to oral regimens. Community pharmacy partnerships through the Indigenous Pharmacy Programmes improve medication management.

Specific conditions

Rheumatic heart disease (RHD) requires secondary prophylaxis with benzathine penicillin G (BPG) 1.2 MU IM every 3–4 weeks for a minimum of 10 years or until age 21 (whichever is longer). RHD registers (e.g., NT RHD Register) facilitate recall and follow-up. The Australian RHD Endgame Strategy targets elimination by 2031.

Referral pathways

Referral through ACCHOs and Aboriginal Hospital Liaison Officers (AHLOs) improves engagement. The Specialist Outreach Assistance Programme provides funded specialist visits to remote communities. NT, WA, and QLD have specific rheumatology outreach programmes targeting Indigenous communities.

📚 References

1. Australian Institute of Health and Welfare (AIHW). Autoimmune disease in Australia. Cat. no. PHE 312. Canberra: AIHW; 2023.
2. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924–939.
3. Fanouriakis A, Kostopoulou M, Alber K, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–745.
4. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2021;73(11):1583–1599.
5. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18.
6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Available from: immunisationhandbook.health.gov.au.
7. Rheumatic Heart Disease Australia (RHDAustralia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
8. Pharmaceutical Benefits Scheme (PBS). PBS Schedule. Australian Government Department of Health. Available from: pbs.gov.au. Accessed 2024.
9. Agarwal S, Cunnington J, Nossent J. Autoimmune disease in Indigenous Australians: a systematic review. Int J Rheum Dis. 2021;24(12):1487–1498.
10. Pisetsky DS. Antinuclear antibody testing — misunderstood or misused? Clin Immunol. 2023;255:109717.
11. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771–1782.
12. Ledingham J, Deighton C; British Society for Rheumatology Standards, Audit and Guidelines Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNFα blockers in adults with rheumatoid arthritis. Rheumatology. 2005;44(2):155–158.
13. National Health and Medical Research Council (NHMRC). National statement on ethical conduct in human research. Canberra: NHMRC; 2023 (updated).

for PBS-listed medicines at participating pharmacies.

Cultural safety

Medication adherence

Specific conditions

Referral pathways

📚 References

1. Australian Institute of Health and Welfare (AIHW). Autoimmune disease in Australia. Cat. no. PHE 312. Canberra: AIHW; 2023.
2. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924–939.
3. Fanouriakis A, Kostopoulou M, Alber K, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–745.
4. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2021;73(11):1583–1599.
5. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18.
6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Available from: immunisationhandbook.health.gov.au.
7. Rheumatic Heart Disease Australia (RHDAustralia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
8. Pharmaceutical Benefits Scheme (PBS). PBS Schedule. Australian Government Department of Health. Available from: pbs.gov.au. Accessed 2024.
9. Agarwal S, Cunnington J, Nossent J. Autoimmune disease in Indigenous Australians: a systematic review. Int J Rheum Dis. 2021;24(12):1487–1498.
10. Pisetsky DS. Antinuclear antibody testing — misunderstood or misused? Clin Immunol. 2023;255:109717.
11. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771–1782.
12. Ledingham J, Deighton C; British Society for Rheumatology Standards, Audit and Guidelines Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNFα blockers in adults with rheumatoid arthritis. Rheumatology. 2005;44(2):155–158.
13. National Health and Medical Research Council (NHMRC). National statement on ethical conduct in human research. Canberra: NHMRC; 2023 (updated).