|
Drug
|
Oral/enteral route STARTING doses by CKD stage
|
Comments
|
|
CKD 1,2
eGFR 60 or above
|
CKD 3
eGFR 30-59
|
CKD 4
eGFR 15-29
|
CKD 5 and dialysis
eGFR less than 15
|
|
Simple analgesia: best given regularly
|
|
|
Paracetamol
|
1g 6 hrly
(max 4g daily)
|
normal
|
normal
|
normal
|
- Caution in liver failure.
- Available PR (poor absorption) and IV.
- Reduce dose if less than 50kg
- Dialyzability: Removed by HD only
|
|
NSAIDs
|
normal
|
normal, but avoid
|
normal, but avoid
|
normal, only use if on dialysis
|
- AVOID if eGFR less than 60ml/min.
- Adverse effects more likely in CKD including: fluid retention; GI bleeding; AKI; cardiotoxicity. Short courses only.
- Clinically significant interactions including: diuretics, ACEi, ARBs
- Dialyzability: Most considered not dialysed
|
|
|
|
|
Weak opioids
|
|
|
|
CKD 1,2
|
CKD 3
|
CKD 4
|
CKD 5 and dialysis
|
|
|
Tramadol (preferred over codeine)
|
50-100mg
6hrly (max 400mg daily)
|
50-100mg 6hrly
|
50mg 6hrly
|
50mg 8hrly
|
- AVOID if eGFR less than 30ml/min. Accumulates in renal impairment. Use cautiously; adjust dose as appropriate and increase dose interval
- Lowers seizure threshold; accumulation may precipitate seizures. Possible adjuvant antidepressant effects. Risk of serotonin syndrome
- Several interactions including carbamazepine and warfarin
- Dialyzability: Removed by HD; not by PD. Watch for rebound pain.
|
|
Codeine
|
30-60mg
4-6 hrly
|
normal
|
30-60mg 6 hrly, but avoid
|
30mg 6 hrly, but avoid
|
- AVOID if eGFR less than 30ml/min. Metabolites can accumulate causing adverse effects. Increased risk of constipation, sedation and narcosis. Use cautiously; adjust dose as appropriate and increase dose interval.
- Individual sensitivity dependent on cytochrome P450-2D6 phenotype
- Dialyzability: Unknown; considered not dialysed. Increased risk of accumulation.
|
|
|
|
|
Strong opioids
|
|
|
|
CKD 1,2
|
CKD 3
|
CKD 4
|
CKD 5 and dialysis
|
|
|
Oxycodone (preferred over morphine)
|
5-10mg 4hrly
|
2.5-5mg 4-6 hrly
|
2.5mg 6 hrly
|
1.25mg 6 hrly
|
- Strong opioid; risk of constipation, sedation, opioid toxicity and dependence
- Metabolites and parent drug can accumulate causing adverse effects. Use cautiously with careful monitoring, adjust dose if necessary. Better tolerated than morphine. Preferred initial opioid if eGFR less than 30ml/min.
- Avoid long-acting preparations
- 5mg oral equivalent to approx. 10mg oral morphine. IV dose 50% of oral
- Dialyzability: Removed by HD; no data for PD. Watch for rebound pain
|
|
Morphine
|
5-10mg 2 hrly
|
5-10mg 4 hrly
|
5mg 4 hrly, but avoid
|
2.5-5mg 4 hrly, but avoid
|
- AVOID if eGFR less than 30ml/min. Active metabolites with long half-life (particularly morphine-6-glucuronide) can accumulate causing increased therapeutic and adverse effects which may persist long after discontinuation
- Strong opioid; risk of constipation, sedation, opioid toxicity and dependence
- Use cautiously; adjust dose as appropriate and increase dose interval. Oxycodone preferred at all CKD stages.
- Avoid long-acting preparations
- IM/IV dose 30% of oral
- Dialyzability: Removed by HD; no data for PD. Watch for rebound pain
|
|
|
|
|
Adjuvant analgesics
|
|
|
|
CKD 1,2
|
CKD 3
|
CKD 4
|
CKD 5 and dialysis
|
|
|
Gabapentin
|
300mg tds, increased as necessary to 900mg tds
|
300mg tds
|
300-600mg daily
|
100mg daily
(increased as necessary to300mg daily)
(or alt die after haemodialysis)
|
- Accumulates in renal impairment and increased risk of CNS depressant effects in CKD; Start at lowest dose, increase dosing interval and uptitrate.
- Adverse effects include: somnolence, ataxia, weight gain, hypo/hyperglycaemia, reversible renal deterioration. May cause false positive dipstick proteinuria.
- Antacids reduce absorption
- Dialyzability: Entirely removed by HD - needs dosing post-HD. Probably removed by PD
|
|
Pregabalin
|
25mg-75mg daily
|
25mg-75mg daily
|
25mg-50mg daily
|
25mg daily
|
- Accumulates in renal impairment and increased risk of CNS depressant effects in CKD; start at lowest dose, increase dosing interval and uptitrate. Not metabolized, 98% of dose excreted unchanged in urine
- Adverse effects include: confusion, somnolence, oedema, risk of abuse and dependence, risk of respiratory depression
- Dialyzability: dialysed by all RRTs. Dose as for GFR <15ml/min
|
|
Amitriptyline
|
10-50mg daily
|
normal
|
normal
|
normal
|
- Antimuscarinic (dry mouth, constipation, urinary retention). Introduce/withdraw gradually (to avoid postural BP change)
- Not considered dialyzable
|
|
Duloxetine
|
30mg at night, titrate up to 120mg per day
|
30mg at night, titrate up to 120mg per day
|
30mg at night, cautious up titration
|
30mg at night, do not titrate up
|
- Antimuscarinic (dry mouth, constipation, urinary retention). Introduce/withdraw gradually (to avoid postural BP change)
- Patients with CKD 5 exhibit high plasma concentrations of duloxetine
- Not considered dialyzable
|
|
|
|
|
On specialist team recommendation only:
|
|
|
|
CKD 1,2
|
CKD 3
|
CKD 4
|
CKD 5 and dialysis
|
|
|
Methadone
|
100%
|
100%
|
100%
|
50%
|
- Strong opioid: risk of constipation, sedation, opioid toxicity and dependence
- Appears safe in renal impairment; metabolites are inactive
- Most commonly used in opioid substitution therapy for opioid dependence, in which case it is safe to be continued
- Long half-life so not appropriate for treating acute pain
- Caution QTc interval prolongation
- Dialyzability: Parent drug is not dialyzed
|
|
Buprenorphine
|
100%
|
100%
|
100%
|
50%
|
- Strong opioid: risk of constipation, sedation, opioid toxicity and dependence, although partial agonist so there is some ceiling effect with doses (both for benefit and adverse effects)
- Appears safe in renal impairment but always start with lowest dose
- Available as sublingual tablet or transdermal patches: BuTrans patches are lower dose (5, 10, 15 or 20mcg/h) and changed weekly, while Transtec patches (35, 52.5 or 70mcg/h) are changed every 4 days.
- Approximate opioid strength: 200mcg sublingual tablet = 8mg oral morphine per dose; 10mcg BuTrans patch = 24mg oral morphine per day
- Sublingual preparations not appropriate for maintenance analgesia; transdermal patch not appropriate for acute or intermittent pain
- Established patches should be continued with caution: long duration of action with effects lasting for 24 hours after patch removal
- High-dose sublingual (Subutex/Suboxone) or subcutaneous modified-release preparations (Buvidal) of buprenorphine are used as opioid substitution therapy in addiction
- Dialyzability: dialysed by all RRTs. Dose as for GFR <15ml/min
|
|
Fentanyl
|
100%
|
100%
|
100%
|
100%
|
- Strong opioid: risk of constipation, sedation, opioid toxicity and dependence
- Appears safe, however a dose reduction is necessary. No active metabolites. Opioid strength is high: 25mcg/h fentanyl patch is equivalent to 60-90mg oral morphine per day
- Established patches should be continued with caution: long duration of action with effects lasting for 24 hours after patch removal
- No oral preparation. Intravenous and sublingual preparations not appropriate for maintenance analgesia; transdermal patch not appropriate for acute or intermittent pain
- Dialyzability: Use caution because parent drug is poorly dialyzable
|
|
Alfentanil
|
100%
|
100%
|
100%
|
100%
|
- Palliative care only
- Opioid of choice for syringe driver use in patients with an eGFR less than 30ml/min
- Doses not affected by renal impairment
- Dialyzability: not removed by dialysis
|
