There is a high prevalence of unpleasant symptoms in patients with kidney disease and there is a growing recognition that these are more difficult to treat in advanced CKD, in those receiving renal replacement therapy and those who choose not to dialyse.

Renal disease and distressing symptoms

We have been using the POS-S renal screening tool for symptom scoring and have developed some pharmacological approaches to managing commonly encountered symptoms.

These have been stratified according to safety in this population.

Drugs are classified in three ways:

  • considered safe in renal failure
  • use with caution
  • avoided where possible in patients with stage 4 and 5 CKD

Efficacy and side effects should always be monitored closely and treatment tailored to the individual.

Patients with troublesome symptoms can be referred to the RMH Renal Supportive Care service through the CKD Nurse Practitioner or to the Palliative Care service.

There is a symptom control clinic at Royal Melbourne Hospital which can be booked by calling the CKD Nurse Practitioner.

The Symptom Control Service at RMH has been kindly supported by the Victorian Department of Health and an unrestricted educational grant from Amgen Australia.

Scoring tools

Australia-modified Karnofsky Performance Status (AKPS) Scale

Clinician ratedDescription
100Normal, no complaints or evidence of disease
90Able to carry on normal activity, minor signs or activity
80

Normal activity with effort, some signs or symptoms of disease

70Care for self, unable to carry on normal activity or to do active work
60Occasional assistance but is able to care for most needs
50Requires considerable assistance and frequent medical care
40

In bed more that 50% of the time

30Almost completely bedfast
20Totally bedfast and requiring nursing care by professionals and / or family
10Comatose or barely rousable

Symptom control guidelines

These symptom control charts were developed by Charmaine Foo, Rosemary Masterson, Jennifer Beavis & Steve Holt as a local response to POS-Renal. These are not exhaustive and, as there is little evidence base, may not all be appropriate for your patient. They were designed for internal use only. We welcome comment and suggestions. The Royal Melbourne Hospital Renal Unit is not responsible for use of these guidelines and use is entirely at the discretion of the treating physician

We welcome constructive feedback - please call or email our CKD Nurse Practitioner in our contact details.

Somatic pain

DrugDosing in CKD 4/5In RRTPrescriptionSafe to use?

Paracetamol

No dose reduction required

No dose reduction

Safe in renal failure

Oxycodone

Start at 50-75% of normal dose – 1-2.5mg PO 4-6hrly/PRN
Some sources advise avoidance in CKD5. Consider increasing dose interval
Convert to buprenorphine or fentanyl once dose requirements known (see fentanyl/buprenorphine below).
MR oxycodone to be avoided if possible, but at low doses consider Oxycodone/naloxone combination (Targin) to minimise constipation

Dose reduction as described

Oxycodone IR (Oxynorm oral liquid) 5mg/5ml [250ml]

Use with caution

Hydromorphone

Start at low end of dose range 0.5-1mg PO 4-6hrly/PRN
Or 0.25-0.5mg SC 4-6hrly/PRN. Consider increasing dose interval
Convert to buprenorphine or fentanyl once dose requirements known (see fentanyl/buprenorphine below).

Dose reduction as described

Hydromorphone IR (Dilaudid oral liquid) 1mg/ml [473ml]

Use with caution

NSAIDs

Ibuprofen 200-400mg tds or diclofenac 25-50mg bd-tds
Use only if anuric and not dependent on residual renal function (e.g. avoid if on PD with significant residual renal function)
Use in conjunction with PPI for gastric protection
Avoid if at high risk of MI
Consider topical NSAID to minimise systemic effect

Not removed by dialysis; dose as described

Ibuprofen 400mg [30]
Diclofenac enteric coated 25mg [50] or 50mg [50]

Use with caution

Fentanyl

Start at 75-100% of normal dose - 25-50mcg SC 1hr/PRN
Lowest dose fentanyl patch of 12mcg/hr roughly equivalent to morphine 40mg/24hrs - may be too high for opioid naïve patients.

Titrate with IR hydromorphone or oxycodone until dose requirements known, then convert to fentanyl patch. Continue hydromorphone or oxycodone (if taking regularly) for 1st 12 hours after patch initiation, will need IR hydromorphone PO, oxycodone PO or fentanyl SC for breakthrough pain thereafter

Not significantly removed by dialysis; dose as described

Fentanyl MR (Durogesic patch)
x mcg/hr [5 patches]

Safe in renal failure

Buprenorphine

Lowest dose of buprenorphine patch of 5mcg/hr roughly equivalent to 10mg PO morphine over 24 hrs

Best for chronic stable pain – if pain unstable, titrate with IR hydromorphone or oxycodone until dose requirements known, then convert to buprenorphine patch. Continue hydromorphone or oxycodone (if taking regularly) for 1st 12 hours after patch initiation, will need IR hydromorphone PO, oxycodone PO or fentanyl SC for breakthrough pain thereafter. *Although buprenorphine is a partial opioid antagonist, this is not of clinical concern at the doses used and alternative opioids for breakthrough pain can be co-prescribed

Dose as described

Buprenorphine MR (Norspan patch)

Y mcg/hr [2 patches]
Safe in renal failure

Methadone

Not renally excreted, but unpredictable pharmacokinetics

Use in conjunction with Chronic Pain or Palliative Care service

Not removed by dialysis

Safe in renal failure

Codeine

Avoid if possible. If necessary limit to 120mg/day

Unknown removal by dialysis

Avoid if possible for stage 4 and 5 CKD patients

Morphine

If absolutely necessary, reduce to 25-50% of normal dose, increase dose interval. Avoid MR preparations, infusions

Not removed by dialysis

Avoid if possible for stage 4 and 5 CKD patients

Tramadol

Avoid if possible. If necessary, max 100mg bd in CKD IV, max 50mg bd in CKD V

Unknown removal by dialysis

Avoid if possible for stage 4 and 5 CKD patients

Notes

  • IR: immediate release
  • MR: modified/slow release
  • Ensure anti-emetics (e.g. metoclopramide 10mg tds/prn or haloperidol 0.5mg bd/prn) and laxatives always co-prescribed with any opioid
  • Always use minimum effective dose

Neuropathic pain

DrugDosing in CKD 4/5In RRTPossible Side EffectsPrescriptionSafe to use?

Nortriptyline

Start at low end of dose range e.g. 10mg PO nocte.
Titrate cautiously

Dose as described

Anticholinergic side effects may exacerbate other symptoms experienced by patients with ESRF e.g. drowsiness, confusion, postural hypotension

Nortriptyline (Allegron tablets) 10mg [50]

Use with caution

Gabapentin

Start at low end of dose range, titrate cautiously.
In CKD 4, max 300-600mg/day

In CKD 5, max 100-600mg/day or alt days

PD/HD -
100-300mg post dialysis

Adverse effects including dizziness, ataxia, drowsiness may be more severe in renal impairment

Some sources advise that it is preferable not to use in conservatively managed ESRF

Gabapentin 100mg [100]

Not PBS listed for neuropathic pain
Use with caution

Pregabalin

In CKD 4, start at 25mg nocte, max 150mg daily in divided doses or nocte

In CKD 5, start at 25mg nocte, max 75mg nocte

PD/HD –

dose of 25-100mg immediately after 4 hr HD session or daily in PD

As with gabapentin

Pregabalin (Lyrica capsules) 100mg [56]

Streamlined authority 4172
Use with caution

Pruritus

DrugDosing in CKD 4/5In RRTPrescriptionSafe to use?

Gaba-linoleic acid

100mg bd = Blackmore’s Evening Primrose Oil (EPO 1000mg = gla 100mg)
1 capsule bd

No dose reduction

Over the counter

Safe in renal failure

Menthol (0.05%) in aqueous cream

Apply PRN

No dose reduction

Compounding pharmacy

Use with caution

Gabapentin

In CKD3, start at 300mg daily; titrate cautiously to max 600mg daily
In CKD4, start at 100mg daily; titrate cautiously to max 300mg daily
In CKD5, start at 100mg alt nights; titrate cautiously to max 300mg alt nights

100-300mg after each HD session or alt/daily on PD

Gabapentin 100mg [100]

Not PBS listed for pruritus
Use with caution

Pregabalin

In CKD3, start at 75mg daily, titrate cautiously to max 300mg in divided doses
In CKD4, start at 25-50mg daily, titrate cautiously to max 150mg nocte or in divided doses
In CKD5, start at 25mg nocte, titrate cautiously to max 75mg nocte

25-100mg after each HD session or daily on PD

Pregabalin (Lyrica capsules)
25mg [56]
Streamlined authority 4172

(not PBS listed for pruritus)
Use with caution

Promethazine

Starting dose 10mg bd - tds, titrate cautiously to max 25mg tds
Risk of sedation, confusion, other anti-cholinergic effects

Not removed by dialysis - dose as described

Promethazine 10mg [50]

Use with caution

Non-pharmacological measures: avoid water, especially hot water. Reduce frequency and duration of bathing; avoid soap and shampoo; use bath oils or soap substitute; avoid vasodilating food and drinks e.g. coffee, alcohol, spices, avoid overheating; keep fingernails short; use cold compresses; use non-fragranced, non-coloured hydrating ointments and creams

Restless legs

DrugDosing in CKD 4/5In RRTPrescriptionSafe to use?

Gabapentin

In CKD 3, start at 300mg daily; titrate cautiously to max 600mg daily
In CKD 4, start at 100mg daily; titrate cautiously to max 300mg daily
In CKD 5, start at 100mg alt nights; titrate cautiously to max 300mg alt nights

100 - 300mg after each HD session

Gabapentin 100mg [100] *Not PBS listed for restless legs

Use with caution

Pregabalin

In CKD3, start at 75mg daily, titrate cautiously to max 300mg in divided doses
In CKD4, start at 25-50mg daily, titrate cautiously to max 150mg nocte or in divided doses
In CKD5, start at 25mg nocte, titrate cautiously to max 75mg nocte

25 - 100mg after each HD session

Pregabalin (Lyrica capsules) 25mg [56] *Not PBS listed for restless legs

Use with caution

Clonazepam

0.5 - 1mg nocte

Not removed by dialysis

Clonazepam (Paxam tablets) 0.5mg [100] *Not PBS listed for restless legs

Use with caution

Pramipexole

Start with 0.125mg 2-3 hours before bedtime, may increase to max 0.75mg/day every 4-7 days. Care in older patients with significant cognitive impairment. Can be discontinued without tapered dose reduction
*PBS listed for severe primary restless legs syndrome who meet 4 diagnostic criteria below, and whose International Restless Legs Syndrome Rating Scale (IRLSRS) score >or = 21 before starting pramipexole (date and score to be documented in medical records)
a) An urge to move legs usually accompanied or caused by unpleasant sensations in legs
b) the urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting
c) The urge to move or unpleasant sensations are partially or totally relived by movement, such as walking or stretching at least as long as the activity continues
d) The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur during the evening or night

Pramipexole (Sifrol tablets) 0.125mg [30]*

Use with caution

Nausea and vomiting

DrugDosing in CKD 4/5In RRTPrescriptionSafe to use?

Metoclopramide

In CKD4, use 75-100% of normal dose 10mg 8hrly
In CKD5, use 50-100% of normal dose – 10mg 8-12hrly

Not removed by dialysis

Metoclopramide tablets 10mg [25]/[100]

Use with caution

Haloperidol

Start at low end of dose range
0.5mg PO/Subcut BD/PRN, titrate cautiously
Increased risk of sedation

Not removed by dialysis

Haloperidol (Serenace tablets) 0.5mg [100]

Use with caution

Cyclizine

No dose adjustment suggested.
Use normal dose of 50mg PO/Subcut tds-qid/PRN

Unknown removal by dialysis

Cyclizine (Valoid tablets) 50mg – requires completion of SAS form

Use with caution

Levomepromazine

In CKD5, reduce from normal doses of 6.25-12.5mg PO/Subcut
Increased risk of sedation
Use in conjunction with palliative care service

Not removed by dialysis

Levomepromazine (Nozinan tablets) 25mg - requires completion of SAS form

Use with caution

Dyspnoea

Drug

Opioids - see somatic pain chart

+/- Low dose benzodiazepines for anxiety associated dyspnoea
e.g. lorazepam 0.5mg sublingually tds/prn

Constipation

DrugDosingPrescriptionCommentsSafe to use?

Docusate sodium 50mg + sennosides 11.27mg (Coloxyl and senna)

Start with 1-2 tablets od-bd
Titrate as required to max 8 tablets/day

[90] max 2 repeats
Available over the counter

Combination of surface-wetting softener and large bowel stimulant

Safe in renal failure

Lactulose mixture

Start with 10-20ml od-bd
Titrate as required

Lactulose mixture 3.34g/5ml [500ml] up to 5 repeats (PBS licensed for palliative care patients or in hepatic coma)
Available over the counter

Hyperosmolar osmotic laxative

Safe in renal failure

Macrogol 3350 - Sodium chloride - Sodium bicarbonate - Potassium chloride (Movicol)

Start with 1-2 sachets od-bd
Max 8 sachets/day

Available over the counter

Iso-osmolar osmotic laxative Note each sachet to be mixed in 125ml of water – impact on fluid balance

Use with caution

Metamucil

Fybogel

Bulking agents
AVOID in renal failure as requires large accompanying fluid intake

Avoid if possible for stage 4 and 5 CKD patients

End of life care

Terminal restlessness

DrugDosing in CKD 4/5Safe to use?

Midazolam

In CKD4, start with normal dose of 2.5-5mg Subcut 2-4hrly/PRN
In CKD5, start with reduced dose of 1-2.5mg Subcut 2-4hrly/PRN.
Consider increasing dose interval

Use with caution

Haloperidol

Start with 0.5 -1mg subcut BD/PRN, titrate cautiously

Use with caution

Levomepromazine

Start with 12.5 - 25mg subcut BD - TDS/PRN
May need to increase dose to 25-50mg
Max dose of 200mg/24hrs
Suggest consulting Palliative Care service

Use with caution

Excess respiratory secretions

DrugDosingSafe to use?

Glycopyrrolate

200mcg Subcut PRN to max of 1.2mg/24hrs
Preferred if patient conscious as does not cross blood brain barrier

Safe in renal failure

Hyoscine butylbromide

20-40mg Subcut PRN to max of 120mg/24 hrs
Preferred if patient conscious as does not cross blood brain barrier

Safe in renal failure

Hyoscine hydrobromide

200-400mcg Subcut PRN to max of 2.4mg/24hrs Crosses blood brain barrier – may increase confusion/sedation

Use with caution