From the FDA Drug Label
Renal disease — In depressed patients on dialysis (N=12), fluoxetine administered as 20 mg once daily for 2 months produced steady–state fluoxetine and norfluoxetine plasma concentrations comparable with those seen in patients with normal renal function While the possibility exists that renally excreted metabolites of fluoxetine may accumulate to higher levels in patients with severe renal dysfunction, use of a lower or less frequent dose is not routinely necessary in renally impaired patients
The FDA drug label does not answer the question.
From the Research
Fluoxetine can generally be used safely in patients with stage 2 chronic kidney disease (CKD) without dose adjustment. For patients with stage 2 CKD (GFR 60-89 mL/min/1.73m²), fluoxetine can be initiated at standard doses, typically 20 mg daily, with the option to increase to 40-80 mg daily if needed based on clinical response. No specific dose reduction is required at this stage of kidney disease as fluoxetine is extensively metabolized by the liver, with less than 10% of the drug excreted unchanged through the kidneys 1. However, patients with CKD should be monitored more closely for side effects such as nausea, headache, insomnia, or increased anxiety, particularly during the initial weeks of treatment. It's also important to be aware that fluoxetine has a long half-life (2-3 days for the parent compound and 7-9 days for its active metabolite norfluoxetine), which means drug accumulation could potentially occur over time even in mild kidney impairment. If the patient has other comorbidities or is taking multiple medications, drug interactions should be carefully evaluated, especially with medications that affect serotonin levels or are highly protein-bound, as fluoxetine may compete for binding sites.
Some studies have investigated the use of antidepressants in patients with CKD, but the evidence is not directly applicable to fluoxetine in stage 2 CKD. For example, a study on sertraline in patients with non-dialysis-dependent CKD found no significant improvement in depressive symptoms compared to placebo 2. However, this study does not provide direct evidence for the use of fluoxetine in stage 2 CKD. Another study on weekly fluoxetine in hemodialysis patients reported that doses up to 180 mg may be effective, but this population is different from those with stage 2 CKD 3.
The pharmacokinetics of fluoxetine are not significantly affected by renal impairment, as shown in a study published in 1993 1 and another in 1994 4. This suggests that fluoxetine can be used safely in patients with stage 2 CKD without dose adjustment. However, it is essential to monitor patients closely for side effects and potential drug interactions.
In summary, fluoxetine can be used safely in patients with stage 2 CKD without dose adjustment, but close monitoring for side effects and potential drug interactions is necessary. The evidence from studies on sertraline and weekly fluoxetine in different populations does not directly apply to fluoxetine in stage 2 CKD, but the pharmacokinetic studies provide reassurance about the safety of fluoxetine in this population 1, 4.