From the Guidelines
Duloxetine should be used with caution in patients with Chronic Kidney Disease (CKD) and impaired renal function, with careful consideration of the benefits versus potential harms, as recommended by the KDIGO 2024 clinical practice guideline 1. When prescribing duloxetine to patients with CKD, it is essential to monitor eGFR, electrolytes, and therapeutic medication levels, when indicated, to minimize the risk of adverse effects 1.
- For mild to moderate CKD (GFR 30-80 mL/min), no dosage adjustment is typically required, but close monitoring is necessary.
- However, for patients with severe renal impairment (GFR <30 mL/min) or end-stage renal disease, duloxetine is generally not recommended due to significantly reduced drug clearance, potentially leading to higher blood levels and increased risk of adverse effects.
- If treatment is deemed necessary in severe CKD, consider starting at a lower dose (such as 20-30 mg daily) with gradual titration while monitoring for side effects like nausea, dizziness, increased blood pressure, or worsening renal function. The concern with duloxetine in renal impairment stems from its extensive hepatic metabolism and the potential accumulation of metabolites that are normally excreted through the kidneys.
- Alternative antidepressants with less renal clearance dependence, such as sertraline or citalopram, might be safer options for patients with advanced kidney disease. It is crucial to weigh the benefits of duloxetine against the potential risks and consider alternative treatment options, as recommended by the Mayo Clinic Proceedings 1.
- Duloxetine has shown efficacy in the treatment of major depression and generalized anxiety disorder, but its use in patients with CKD requires careful consideration and monitoring 1.
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 prescribing of selective serotonin reuptake inhibitors (SSRIs) to middle-aged and older patients found that lower kidney function was moderately associated with a reduced SSRI dose, independently of age, but did not specifically address duloxetine 5.
- The clinical pharmacokinetics and drug interactions of duloxetine have been reviewed, and it was found that impaired hepatic function or severely impaired renal function warrant specific warnings or dose recommendations 6.
- In general, patients with CKD require special consideration when prescribed medications that are eliminated primarily by renal filtration, and dosage adjustments may be necessary to avoid toxicity 7.