Should morphine, metoprolol, losartan, hydrocodone/acetaminophen, or canagliflozin be adjusted for renal insufficiency?

Dose Adjustments for Renal Insufficiency

Among the medications listed, morphine, losartan, and canagliflozin require dose adjustments in renal insufficiency, while metoprolol does not require adjustment, and hydrocodone/acetaminophen should be used with extreme caution due to accumulation of toxic metabolites.

Morphine

• Start with lower than usual doses and titrate slowly in patients with renal impairment, as morphine pharmacokinetics are significantly altered in renal failure 1
• Monitor closely for signs of respiratory depression, sedation, and hypotension during dose titration 1
• The active metabolite morphine-6-glucuronide accumulates in renal insufficiency and can cause prolonged respiratory depression 2

Metoprolol

• No dose adjustment is required for metoprolol in patients with renal impairment 3
• Metoprolol undergoes primarily hepatic metabolism, making it safe to use at standard doses regardless of kidney function 3
• However, initiate at low doses in elderly patients who may have concurrent renal and hepatic dysfunction 3

Losartan

• No dose adjustment is necessary in patients with renal impairment unless the patient is also volume depleted 4
• However, avoid use in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m² 4
• Monitor electrolytes and serum creatinine regularly, as recommended for all RAAS blockers in chronic kidney disease 5
• Temporarily discontinue during acute illness that increases risk of acute kidney injury in patients with eGFR <60 mL/min/1.73 m² 5

Hydrocodone/Acetaminophen

• Use with extreme caution in renal insufficiency, as opioid metabolites accumulate and acetaminophen clearance may be reduced 2
• Start with reduced doses (similar to morphine recommendations) and extend dosing intervals 1, 2
• Monitor for excessive sedation, respiratory depression, and signs of opioid toxicity 1
• Consider alternative analgesics when possible in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) 2

Canagliflozin

• Limit to 100 mg daily if eGFR 45-59 mL/min/1.73 m² 5
• Avoid initiating and discontinue if eGFR persistently <45 mL/min/1.73 m² 5
• Contraindicated in patients on dialysis or with eGFR <30 mL/min/1.73 m² 5
• SGLT2 inhibitors are not expected to be effective for glycemic control in advanced chronic kidney disease 5

Key Clinical Considerations

Monitoring Requirements

• Calculate creatinine clearance or eGFR before initiating any of these medications 5, 6
• Reassess renal function regularly, especially during acute illness or when adding nephrotoxic agents 5
• For drugs with narrow therapeutic ranges (like opioids), consider therapeutic drug monitoring when available 7

Common Pitfalls to Avoid

• Do not switch between anticoagulants or adjust multiple renally-cleared drugs simultaneously without careful monitoring, as this increases bleeding and toxicity risk 5
• Avoid NSAIDs and other nephrotoxins in patients already on renally-cleared medications, as this compounds toxicity risk 5, 2
• Do not rely solely on serum creatinine - it can be misleading in elderly patients with low muscle mass; always calculate eGFR or creatinine clearance 5, 6
• Ensure adequate hydration before administering potentially nephrotoxic agents to minimize further renal injury 2

Special Populations

• In elderly patients (≥65 years), start with lower doses even when calculated eGFR suggests normal function, as they have increased sensitivity to opioids and other medications 1, 3
• In patients with both hepatic and renal impairment, exercise additional caution with morphine and metoprolol, starting at the lowest possible doses 1, 3