Analgesia in Patients with Renal Disease

Many analgesics are excreted by the kidneys and any degree of renal impairment can reduce drug clearance, and therefore the dose of drug required. Glomerular filtration rate (GFR) gives an indication of how much drug clearance will be affected by renal impairment. Renal dysfunction can also influence the absorption, metabolism, distribution and pharmacodynamics of many drugs.

End Stage Renal Disease (ESRD) correlates to:

  • GFR of less than 15mL/min or
  • Stage 5 (UK CKD Guidelines 2005)

Patients with GFR 15-29mls/min (Stage 4) will also be more safely managed with medication dose reductions recommended for Stage 5 disease.

In general when prescribing analgesics in ESRD:

  • immediate release preparations are safer than sustained/ modified/ controlled release preparations
  • p.r.n. (as required) prescriptions are safer than regular prescriptions
  • extended dose intervals are better tolerated

WHO Ladder Step 1 analgesics

Paracetamol

Generally safe.

Metabolism: Extensively metabolised by liver

Dose adjustments: Maximum 3g/24hrs. Minimum dose interval 6hrs.

Comments: Avoid effervescent tablets (high sodium content)

NSAIDS

Avoid (unless risk of deteriorating renal function outweighed by need for NSAID analgesia or patient is on dialysis).

Metabolism: Inhibits COX in kidney. Excreted mainly by liver.

Comments: Can cause severe and irreversible reduction in GFR. Avoid in renal failure.

WHO Ladder Step 2 analgesics

N.B. No opioid is completely safe in ESRD: All patients with renal impairment should be monitored for signs of opioid toxicity: respiratory depression, myoclonic jerks, drowsiness, confusion, hallucinations, agitation.

Codeine

Avoid

Metabolism: Metabolites excreted by the kidneys and accumulate.

Tramadol

Generally tolerated at reduced doses.

Metabolism: Metabolised by the liver. Excreted in urine.

Dose adjustments: Dose reduction required in patients over 75 years and in renal failure.

GFR less than 30ml/min at dose of 50-100mg BD PO
GFR less than 10ml/min at dose of 50mg
BD PO (50mg QDS PO if on dialysis)

Comments: Use immediate release preparation.

Generally has fewer opioid side effects than other opioids at an equivalent dose.

WHO Ladder Step 3 analgesics

N.B. No opioid is completely safe in ESRD: Patients should be monitored for signs of opioid toxicity when commencing any strong opioid. e.g. respiratory depression, myoclonic jerks, drowsiness, confusion, hallucinations, agitation. See page 15 for dose conversions and seek specialist advice.

Alfentanil

Suitable parenteral opioid for use in advanced renal disease.

Metabolism: Extensively metabolised in the liver.

Dose adjustments: No change in dose required. See conversions in Pain Chapter.

Comments: Can be given via s.c. syringe driver/pump. Short duration of action limits its use for breakthrough analgesia.

Buprenorphine

Use with caution.

Metabolism: Metabolised in liver but metabolites, excreted in the urine.

Dose adjustments: Limited data. Use lowest dose possible.

Comments: Available as transdermal patch and sublingually. Accumulation of metabolites in renal failure may cause respiratory depression.

Fentanyl

Suitable parenteral opioid for use in advanced renal disease.

It is not advisable to use immediate release fentanyl preparations in patients who are naive to step 3 opioids. Seek specialist advice.

Metabolism: 90 % metabolised in the liver.

Dose adjustments: Does not appear to significantly accumulate in renal failure. Use according to guidelines for non- renal failure patients. (see Pain Chapter)

Comments: Available as immediate release preparations and as a transdermal patch.
(Can be given s.c. via a syringe driver/pump but the more soluble Alfentanil may be preferable if large dose volumes of Fentanyl are required)

Hydromorphone

Use with caution.

Metabolism: Primarily metabolised in the liver but excreted in the urine.

Dose adjustments: Use immediate release preparation 4–6 hourly initially and titrate cautiously. Remember that the lowest oral dose is 1.3mg which is equivalent to 10mg morphine.

Comments: Theoretically may cause similar problems to morphine but in practice often better tolerated than morphine. Available in immediate release and slow release oral preparations and s.c.

Oxycodone

Use with caution. Avoid in stage 5 CKD.

Metabolism: Eliminated mainly by the liver, 10% excreted unchanged in urine.

Dose adjustments: If used, start with smallest dose possible in an immediate release preparation. Consider extending dose interval.

Comments: Elimination half-life is prolonged, therefore may accumulate in advanced renal disease.

Methadone

Use by experienced clinician only.

Metabolism: Metabolised in liver. Excreted mainly in faeces

Dose adjustments: Significant individual variation makes titration of doses difficult as in patients with normal renal function.

Comments: May be a useful alternative to other opioids in advanced renal disease BUT requires specialist supervision.

Morphine

Not well tolerated. Avoid if possible.

Metabolism: Major metabolite (morphine-3-glucuronide) excreted by kidneys and accumulates in renal failure.

Dose adjustments: If necessary to use, start with an immediate release preparation in small doses. E.g. 1.25–2.5mg every 4 to 6 hours.

Comments: Likely to cause toxicity and have a longer duration of action. Not well tolerated in patients with advanced renal disease.

Diamorphine

Not well tolerated. Avoid if possible.

Metabolism: Metabolised to morphine.

Dose adjustments: If necessary to use, start with small doses e.g. 1.25 – 2.5mg every 4 to 6 hours.

Comments: Likely to cause toxicity and have a longer duration of action. Not well tolerated in patients with advanced renal disease.

Adjuvant analgesics for Neuropathic Pain

Tricyclic

Antidepressants.

Metabolism: Metabolised by the liver.

Dose adjustments: Dose reduction is not usually necessary in renal failure.

Comments: Start with low doses e.g. amitriptyline 10 to 25mg, increasing slowly. Beware increased risk of cardiovascular side effects in patients with renal impairment.

Anticonvulsants

Carbamazepine.

Metabolism: Metabolised by the liver.

Dose adjustments: No dose adjustment required. Commence at 200mg daily.

Comments: Usually well tolerated.

Gabapentin

Use with caution.

Metabolism: Excreted unchanged by the kidneys.

Dose adjustments: Dose depends on GFR: if GFR <15 max 300mg OD if GFR 15-29 max 300mg BD.

Comments: May accumulate in renal failure.

Pregabalin

Use with caution.

Metabolism: Excreted unchanged by the kidneys.

Dose adjustments: Dose depends on GFR: if GFR <15 max dose 75mg OD if GFR 15–29 max. dose 150mg OD.

Comments: May accumulate in renal failure.

Sodium Valproate

Metabolism: Metabolised by the liver and eliminated by the kidneys.

Dose adjustments: No dose adjustment required. Commence at 200mg daily.

Comments: Usually well tolerated.

Clonazepam

Metabolism: Metabolised by the liver eliminated by the kidneys.

Dose adjustments: 0.5mg to 1mg nocte PO/SC.

Comments: May accumulate in renal failure.

DISCLAIMER

This Guide is intended for use by healthcare professionals and the expectation is that they will use clinical judgement, medical, and nursing knowledge in applying the general principles and recommendations contained within. They are not meant to replace the many available texts on the subject of palliative care.
Some of the management strategies describe the use of drugs outside their licensed indications. They are, however, established and accepted good practice. Please refer to the current BNF for further guidance.
While WMPCPS takes every care to compile accurate information , we cannot guarantee its correctness and completeness and it is subject to change. We do not accept responsibility for any loss, damage or expense resulting from the use of this information.