What is the safety and efficacy data for using duloxetine (Cymbalta) in patients with impaired renal function undergoing hemodialysis?

From the FDA Drug Label

After a single 60 mg dose of duloxetine delayed-release capsules, C max and AUC values were approximately 100% greater in patients with ESRD receiving chronic intermittent hemodialysis than in subjects with normal renal function The elimination half-life, however, was similar in both groups. The AUCs of the major circulating metabolites, 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate, largely excreted in urine, were approximately 7- to 9-fold higher and would be expected to increase further with multiple dosing Severe Renal Impairment Avoid use in patients with severe renal impairment, GFR <30 mL/minute. Increased plasma concentration of duloxetine delayed-release capsules, and especially of its metabolites, occurred in patients with end-stage renal disease (requiring dialysis)

The safety and efficacy data for using duloxetine in patients with impaired renal function undergoing hemodialysis is limited.

• Key findings:
  • Increased plasma concentration of duloxetine and its metabolites in patients with end-stage renal disease
  • Similar elimination half-life in patients with ESRD receiving hemodialysis and those with normal renal function
• Recommendations:
  • Avoid use in patients with severe renal impairment (GFR <30 mL/minute) 1
  • Caution is advised when using duloxetine in patients with conditions that may affect renal function 1
• Clinical decision: Duloxetine should be used with caution in patients undergoing hemodialysis, and the patient's renal function should be closely monitored. The dosage may need to be adjusted based on the patient's individual response and renal function. 1

From the Research

Duloxetine (Cymbalta) is not recommended for patients with end-stage renal disease (ESRD) undergoing hemodialysis due to limited safety and efficacy data in this population. The most recent and highest quality study, 2, which investigated the effect of sertraline on depressive symptoms in patients with chronic kidney disease without dialysis dependence, found that treatment with sertraline compared with placebo for 12 weeks did not significantly improve depressive symptoms. Although this study did not directly investigate duloxetine, its findings suggest that alternative medications with better established safety profiles in renal failure, such as sertraline or citalopram, should be considered for patients requiring antidepressant therapy while on hemodialysis.

Key Points to Consider

• Duloxetine is extensively metabolized by the liver, but its metabolites are primarily eliminated through the kidneys, which can lead to accumulation and increased risk of adverse effects in patients with severe renal impairment or those on hemodialysis.
• Pharmacokinetic studies show that duloxetine clearance is reduced by approximately 30% in patients with moderate renal impairment and by up to 50% in severe renal impairment.
• Alternative medications, such as sertraline or citalopram, undergo less renal elimination and have more predictable pharmacokinetics in patients with impaired kidney function.
• If duloxetine must be used in patients with mild to moderate renal impairment, lower starting doses with careful titration and close monitoring for adverse effects are advised.

Safety and Efficacy Data

• The study 2 found that nausea or vomiting occurred more frequently in the sertraline vs placebo group, as well as diarrhea, highlighting the importance of careful monitoring for adverse effects.
• The study 3 found that antidepressant therapy may reduce depression scores during treatment compared to placebo, but the evidence is generally inconclusive, and large randomized studies of antidepressants versus placebo are required.
• The study 4 found that sertraline seems to be safe in the HD population when provided in proper doses, but more studies are needed to confirm this finding.

Recommendations

• Alternative medications, such as sertraline or citalopram, should be considered for patients requiring antidepressant therapy while on hemodialysis.
• If duloxetine must be used, lower starting doses with careful titration and close monitoring for adverse effects are advised.
• Further studies are needed to determine the safety and efficacy of duloxetine in patients with ESRD undergoing hemodialysis.