SAFE ANALGESIC USE IN CHRONIC

KIDNEY DISEASE

Ma Yuet Ting, BCACP

Senior Pharmacist

Khoo Teck Puat Hospital

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Doctor, I’m

in Pain!

Outline

• Common analgesics in CKD • Paracetamol

• NSAIDs & Cox-2 Inhibitors

• Weak opioids

• Adjuvants • Neuropathic

• Gout

• Arthritis

• Approach to analgesic selection in CKD

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Pain in Chronic Kidney Disease

• Multi-factorial

• Nociceptive, neuropathic, inflammatory

• Under-prescription of analgesics vs. unawareness about

nephrotoxicity

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Rifkin et al. Analgesic Therapy in Patients with Chronic Kidney Disease : A Case-Based Approach

Pain in Chronic Kidney Disease

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Case 1

Mr Tan Wee Teck sees you complaining of mild to moderate back pain. He has not tried anything besides Tiger Balm plaster.

Past medical history include chronic kidney disease.

Which would you prescribe him?

A. Ibuprofen 400 mg TDS

B. Paracetamol 1g every 4–6 hours strictly

C. Tramadol 50 mg TDS

D. Celecoxib 200 mg BD

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Case 1

Mr Tan Wee Teck sees you complaining of mild to moderate back pain. He has not tried anything besides Tiger Balm plaster.

Past medical history include chronic kidney disease.

Which would you prescribe him?

A. Ibuprofen 400 mg TDS

B. Paracetamol 1g every 4–6 hours strictly

C. Tramadol 50 mg TDS

D. Celecoxib 200 mg BD

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COMMON ANALGESICS:

ARE THEY SAFE IN CHRONIC

KIDNEY DISEASE?

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WHO Pain Ladder 8

• Consider in CKD

• Regular dosing

intervals

• Pain intensity

• Dose individualisation

• Giving patients

sufficient details for

proper administration

Paracetamol in CKD

• Drug of choice for mild-moderate pain

• KDIGO: Effective & safe for nociceptive pain (1A)

• Mild anti-inflammatory properties

• Dose: safe at 1g every 8 hours (Max 3g/day)

• Undergoes hepatic metabolism

• Metabolites excreted via urine

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Case 2

Mdm XYZ was admitted to the hospital due to

acute on chronic renal failure secondary to

NSAID use.

Q: How much do you think is her estimated

hospital bill size for a 3.5-day stay??

A: $1200

B: $2400

C: $3600

D: $4200

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Case 2

Mdm XYZ was admitted to the hospital due to

acute on chronic renal failure secondary to

NSAID use.

Q: How much do you think is her estimated

hospital bill size for a 3.5-day stay??

A: $1200

B: $2400

C: $3600

D: $4200 (based on $1200/day)

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Traditional NSAIDs in CKD

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Traditional NSAIDs in CKD

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Traditional NSAIDs in CKD

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NSAID use associated with ↑ risk of CKD

Traditional NSAIDs in CKD

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↑ blood pressure

↑ risk of hyperkalemia

↑ risk of acute kidney injury

↑ risk of GI bleeding if urea is raised in advanced CKD

Traditional NSAIDs in CKD

• Risk factors for acute kidney injury are additive

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Traditional NSAIDs in CKD

• Predisposing factors for NSAID-induced AKI

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1. Heart failure

2. Dehydration

3. CKD

4. ACE-I/ARB, diuretics

5. Elderly

Traditional NSAIDs in CKD

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Avoid NSAIDs in Stage 4 or higher CKD (eGFR<30ml/min)

• AKI can occur with a single dose

Use cautiously in early CKD for short-term pain

• Determine pre-disposing factors for NSAID-induced AKI

• Consider shorter-acting agents at lowest effective dose

• Use for the shortest period of time & continuously review need

• Educate your patients about risks

No NSAID is safer than the others in terms of nephrotoxicity

Case 3

Which of your patients below would be at highest risk for developing AKI from NSAID use?

• A: 70-year-old woman with CKD Stage 3b and

congestive heart failure, on Lisinopril 40 mg OM and frusemide 80 mg BD

• B: 55-year-old woman with CKD Stage 2 with microalbuminuria, currently not on chronic medications

• C: 65-year-old woman with CKD Stage 3b and diabetes on Lisinopril 2.5mg OM

• D: 70-year-old man with hyperlipidemia and hypertension, on Nifedipine LA (Adalat) 30mg OM and Simvastatin 10mg ON

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Case 3

• Answer: Patient A

• 1. Elderly

• 2. Stage 3b CKD (eGFR 30-44 ml/min)

• 2. CHF induce renin production and increase her risk for

hemodynamically mediated AKI

• 4. High dose of lisinopril (dilates the efferent arteriole)

• 5. Frusemide (decreases intravascular volume)

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Cox-2 Inhibitors: Not Any Safer than

NSAIDs in CKD • Risk of AKI similar to traditional NSAIDs

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Cox-2 Inhibitors: Not Any Safer than NSAIDs

in CKD

• Often prescribed due to better GI tolerability

• Not validated in CKD population

• Similar risk of reducing renal perfusion and and

promoting other adverse renal effects

• CKD population excluded from Cox-2 Inhibitor trials

• $$$$

• Hence no benefit of choosing a Cox-2 Inhibitor

over NSAID in CKD patients!

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Tramadol & Codeine in CKD

• Tramadol:

• 50mg BD in eGFR <30ml/min

• Metabolised in liver and excreted by kidney

• Seizures & respiratory depression, max <200mg/day

• Codeine: prolonged half-life in CKD

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Pham et al. Pain Management in Patients with Chronic Kidney Disease. Clinical Kidney Journal Vol 2 (2) -

ADJUVANTS IN PAIN MANAGEMENT:

ARE THEY SAFE IN CHRONIC

KIDNEY DISEASE?

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Osteoarthritis

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• Mild pain: Acetaminophen

• Moderate to severe: NSAIDs, Tramadol

General population

• Mild pain: Acetaminophen

• Moderate to severe: Tramadol

CKD

Case 4

Mr Ahmad sees you today for an acute gout attack. He is 60kg, 50-

year-old with CKD (eGFR 24). His diet includes large amounts of daily

alcohol, red meat and seafood. He’s allergic to paracetamol.

Which is most appropriate in treatment of his acute gout?

•A. Naproxen 550mg BD for 5 days

•B. Allopurinol 100mg OM for 5 days

•C. Prednisolone 30mg OM for 5 days

•D. Colchicine 500mcg QDS for 5 days

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Case 4

Mr Ahmad sees you today for an acute gout attack. He is 60kg, 50-

year-old with CKD (eGFR 24). His diet includes large amounts of daily

alcohol, red meat and seafood. He’s allergic to paracetamol.

Which is the most appropriate in treatment of his acute gout?

•A. Naproxen 550mg BD for 5 days

•B. Allopurinol 100mg OM for 5 days

•C. Prednisolone 30mg OM for 5 days

•D. Colchicine 500mcg QDS for 5 days

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Acute Gout

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• Naproxen, indomethacin

• Colchicine

• Prednisolone

• Chronic gout prophylaxis:

• Initiate allopurinol 100mg/day (Max: 800mg/day)

General population

• Colchicine: 500mcg OD-BD, do not repeat more frequently than 14 days

• *PO prednisolone:

• 0.5 mg/kg/day for 5 to 10 days

• Chronic gout prophylaxis: Initiate Allopurinol 50-100mg/day (Max: 100mg/day)

CKD

Case 5

• You see Mdm Devi, a 70-year-old patient with history of long-standing diabetes and CKD stage 4. She is new to your clinic.

• She has tingling in the hands and feet and sometimes have sharp pain. You suspect diabetic neuropathy.

• Which of the following adjuvants would you consider and what dose would you initiate at?

• A. Gabapentin 300mg ON

• B. Gabapentin 300mg TDS

• C. Pregabalin 75mg BD

• D. Pregabalin 75mg ON

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Case 5

• You see Mdm Devi, a 70-year-old patient with history of long-standing diabetes and CKD stage 4. She is new to your clinic.

• She has tingling in the hands and feet and sometimes have sharp pain. You suspect diabetic neuropathy.

• Which of the following adjuvants would you consider and what dose would you initiate at?

• A. Gabapentin 300mg ON

• B. Gabapentin 300mg TDS

• C. Pregabalin 75mg BD

• D. Pregabalin 75mg ON

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Neuropathic Pain

• Start low, go slow. Dose-adjust

• Gabapentin: Dose-adjust by eGFR

• eGFR <30: 200 – 700mg once daily

• eGFR <15: 100 – 300mg once daily

• Dialysis: 300mg every other night

• Pregabalin: eGFR <30: 25-150mg in 1-2 divided doses

• Amitriptyline, nortriptyline

• May accumulate in CKD

• More side effects (anti-cholinergic, CNS, GI, rarely arrhythmias)

• Several weeks to see maximal analgesic effect

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Choosing an Analgesic in CKD

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Actively screen for:

Old age, CKD, HF, allergies, current & recent medications

Pain = duration/onset,

aggravating factors, severity, function, location, quality

Choose least nephrotoxic agent

Begin with lower dose and dose-adjust

according to eGFR

Consider referring to pain specialist

THANK YOU ma.yuet.ting@alexandrahealth.com.sg

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