SAFE ANALGESIC USE IN CHRONIC KIDNEY DISEASE

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1 1 Doctor, I m in Pain! SAFE ANALGESIC USE IN CHRONIC KIDNEY DISEASE Ma Yuet Ting, BCACP Senior Pharmacist Khoo Teck Puat Hospital

2 2 Outline Common analgesics in CKD Paracetamol NSAIDs & Cox-2 Inhibitors Weak opioids Adjuvants Neuropathic Gout Arthritis Approach to analgesic selection in CKD

3 3 Pain in Chronic Kidney Disease Multi-factorial Nociceptive, neuropathic, inflammatory Under-prescription of analgesics vs. unawareness about nephrotoxicity Rifkin et al. Analgesic Therapy in Patients with Chronic Kidney Disease : A Case-Based Approach

4 Pain in Chronic Kidney Disease 4

5 5 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

6 6 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

7 7 COMMON ANALGESICS: ARE THEY SAFE IN CHRONIC KIDNEY DISEASE?

8 WHO Pain Ladder 8 Consider in CKD Regular dosing intervals Pain intensity Dose individualisation Giving patients sufficient details for proper administration

9 9 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

10 10 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

11 11 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)

12 Traditional NSAIDs in CKD 12

13 Traditional NSAIDs in CKD 13

14 14 Traditional NSAIDs in CKD NSAID use associated with risk of CKD

15 15 Traditional NSAIDs in CKD blood pressure risk of hyperkalemia risk of acute kidney injury risk of GI bleeding if urea is raised in advanced CKD

16 16 Traditional NSAIDs in CKD Risk factors for acute kidney injury are additive

17 17 Traditional NSAIDs in CKD Predisposing factors for NSAID-induced AKI 1. Heart failure 2. Dehydration 3. CKD 4. ACE-I/ARB, diuretics 5. Elderly

18 18 Traditional NSAIDs in CKD 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

19 19 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

20 20 Case 3 Answer: Patient A 1. Elderly 2. Stage 3b CKD (egfr 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)

21 Cox-2 Inhibitors: Not Any Safer than NSAIDs in CKD Risk of AKI similar to traditional NSAIDs 21

22 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! 22

23 23 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 Pham et al. Pain Management in Patients with Chronic Kidney Disease. Clinical Kidney Journal Vol 2 (2) -

24 24 ADJUVANTS IN PAIN MANAGEMENT: ARE THEY SAFE IN CHRONIC KIDNEY DISEASE?

25 25 Osteoarthritis Mild pain: Acetaminophen Moderate to severe: NSAIDs, Tramadol General population Mild pain: Acetaminophen Moderate to severe: Tramadol CKD

26 26 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

27 27 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

28 28 Acute Gout 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 mg/day (Max: 100mg/day) CKD

29 29 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

30 30 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

31 31 Neuropathic Pain Start low, go slow. Dose-adjust Gabapentin: Dose-adjust by egfr egfr <30: mg once daily egfr <15: mg once daily Dialysis: 300mg every other night Pregabalin: egfr <30: mg 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

32 32 Choosing an Analgesic in CKD 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

33 33 THANK YOU

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