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. 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 Severe Renal Impairment Avoid use in patients with severe renal impairment, GFR <30 mL/minute.
Duloxetine Renal Adjustment:
- For patients with end-stage renal disease (ESRD), the dose should not be exceeded, and caution is advised.
- For patients with severe renal impairment (GFR <30 mL/minute), avoid use.
- For patients with mild to moderate degrees of renal impairment (estimated CrCl 30 to 80 mL/min), no significant effect on duloxetine apparent clearance is expected, and no dosage adjustment is necessary. 1
From the Research
Cymbalta (duloxetine) requires dose adjustment in patients with severe renal impairment, but not for mild to moderate renal impairment. For patients with mild to moderate renal impairment (creatinine clearance 30-80 mL/min), no dose adjustment is needed, as shown in a study published in Clinical Pharmacokinetics 2. However, for severe renal impairment (creatinine clearance less than 30 mL/min) or end-stage renal disease, Cymbalta is not recommended due to the potential accumulation of its metabolites to toxic levels, which can increase the risk of adverse effects such as nausea, dizziness, and increased blood pressure. The study found that the maximum plasma concentration and area under the plasma concentration-time curve of duloxetine were approximately 2-fold higher in subjects with end-stage renal disease than in healthy subjects, reflecting an increase in oral bioavailability 2. It is essential to monitor renal function before starting Cymbalta and periodically during treatment, especially in elderly patients or those with known kidney issues, as renal function can change over time. Alternative medications with better renal safety profiles should be considered if treatment is necessary for patients with severe renal impairment. Other studies, such as those published in CNS Drugs 3 and American Journal of Health-System Pharmacy 4, provide additional information on the pharmacology and pharmacokinetics of duloxetine, but the most relevant and recent study for renal adjustment is the one published in Clinical Pharmacokinetics 2. More recent studies, such as those published in Kidney International Reports 5 and Pharmaceutics 6, focus on different aspects of medication dosing in patients with renal impairment, but do not provide more up-to-date information on duloxetine dosing adjustments. Therefore, the recommendation is based on the study published in Clinical Pharmacokinetics 2, which provides the most relevant information on duloxetine pharmacokinetics in patients with renal impairment. Key points to consider when prescribing Cymbalta to patients with renal impairment include:
- Monitoring renal function before and during treatment
- Avoiding use in patients with severe renal impairment or end-stage renal disease
- Considering alternative medications with better renal safety profiles
- Being aware of the potential for adverse effects due to metabolite accumulation in patients with compromised renal function.