From the Guidelines
Duloxetine should be used with caution in patients with chronic kidney disease (CKD) and decreased renal function, and the decision to prescribe should be based on a careful assessment of the potential benefits and risks, with consideration of alternative treatment options and close monitoring of renal function and adverse effects. For patients with mild to moderate renal impairment (creatinine clearance 30-80 mL/min), no dose adjustment is typically needed, as suggested by the general principles of pharmacotherapy in patients with CKD 1. However, duloxetine is not recommended for patients with severe renal impairment (creatinine clearance less than 30 mL/min) or end-stage renal disease (ESRD) requiring dialysis, due to the potential accumulation of duloxetine and its metabolites in patients with significantly reduced renal function, which could increase the risk of adverse effects such as nausea, dizziness, somnolence, and increased blood pressure 1. The drug is primarily metabolized by the liver and eliminated through the kidneys, with approximately 70% of the dose appearing in the urine as metabolites. If duloxetine must be used in patients with moderate renal impairment, start with a lower dose (such as 30 mg once daily) and monitor closely for side effects before considering dose escalation, as recommended by the KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease 1. Regular monitoring of renal function and assessment for adverse effects is essential when prescribing duloxetine to any patient with kidney disease, and consideration should be given to the use of alternative medications with more favorable pharmacokinetic profiles in patients with CKD, as suggested by the European Society of Cardiology working group on cardiovascular pharmacotherapy 1. Key considerations in the management of patients with CKD include the potential for nephrotoxic effects of medications, the need for monitoring of eGFR, electrolytes, and therapeutic medication levels, and the importance of reviewing and limiting the use of over-the-counter medicines and dietary or herbal remedies that may be harmful for people with CKD, as outlined in the KDIGO 2024 clinical practice guideline 1. In terms of specific guidance on the use of duloxetine in patients with CKD, the most recent and highest quality study suggests that caution is needed when prescribing this medication to patients with decreased renal function, and that alternative treatment options should be considered, as recommended by the Mayo Clinic Proceedings 1. Overall, the use of duloxetine in patients with CKD requires careful consideration of the potential benefits and risks, and close monitoring of renal function and adverse effects, as suggested by the European Society of Cardiology working group on cardiovascular pharmacotherapy 1 and the KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease 1.
Some key points to consider when prescribing duloxetine to patients with CKD include:
- The potential for accumulation of duloxetine and its metabolites in patients with significantly reduced renal function, which could increase the risk of adverse effects
- The need for monitoring of renal function and adverse effects in patients with CKD
- The importance of considering alternative treatment options with more favorable pharmacokinetic profiles in patients with CKD
- The need for careful assessment of the potential benefits and risks of duloxetine in patients with CKD, and close monitoring of renal function and adverse effects. It is also important to note that the pharmacokinetics of duloxetine may be affected by age-related changes, such as decreased renal mass and renal blood flow, and increased renal diseases that decrease renal function, as outlined in the European Heart Journal 1. Therefore, duloxetine should be used with caution in patients with CKD, and the decision to prescribe should be based on a careful assessment of the potential benefits and risks, with consideration of alternative treatment options and close monitoring of renal function and adverse effects.
From the FDA Drug Label
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) Limited data are available on the effects of duloxetine delayed-release capsules in patients with end-stage renal disease (ESRD). 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 Population PK analyses suggest that mild to moderate degrees of renal impairment (estimated CrCl 30 to 80 mL/min) have no significant effect on duloxetine apparent clearance
Duloxetine use in patients with CKD is cautioned against, especially in those with severe renal impairment (GFR <30 mL/minute).
- For patients with mild to moderate renal impairment (GFR 30-80 mL/min), there is no significant effect on duloxetine apparent clearance.
- However, for patients with severe renal impairment (GFR <30 mL/minute), use of duloxetine is avoided due to increased plasma concentration of duloxetine and its metabolites.
- In patients with end-stage renal disease (ESRD), duloxetine plasma concentrations are significantly increased, which may lead to adverse effects 2 2.
From the Research
Duloxetine Administration in Patients with Chronic Kidney Disease (CKD)
- Duloxetine is a medication that can be affected by renal impairment, as its metabolites are renally excreted 3.
- A study found that mild or moderate renal impairment does not have a statistically significant effect on the pharmacokinetic parameters of duloxetine, and dose adjustments are not necessary for patients with mild or moderate renal impairment (CL(CR) ≥ 30 mL/min) 3.
- However, for patients with end-stage renal disease (ESRD) or severe renal impairment (CL(CR) < 30 mL/min), exposures of duloxetine and its metabolites are expected to increase, and duloxetine is not generally recommended for these patients 3.
- Another study discussed the management of duloxetine in patients with common acute and chronic medical comorbidities, including acute kidney injury and chronic hepatic dysfunction, but did not provide specific guidance on dose adjustments for patients with CKD 4.
- A study on the pharmacological properties of duloxetine found that impaired renal function is one of the factors that may impact the pharmacokinetics of duloxetine, but only severely impaired renal function warrants specific warnings or dose recommendations 5.
- In general, patients with CKD require special consideration when prescribed medications that are eliminated primarily by renal filtration, as the clearance of these drugs is decreased by renal disease 6.
Key Considerations for Duloxetine Dosing in CKD Patients
- Patients with mild or moderate renal impairment (CL(CR) ≥ 30 mL/min) do not require dose adjustments 3.
- Patients with ESRD or severe renal impairment (CL(CR) < 30 mL/min) should not be prescribed duloxetine due to increased exposures of duloxetine and its metabolites 3.
- Physicians and pharmacists should work together to ensure safe drug prescribing and dosage adjustments for patients with CKD 6.