Is aripiprazole safe in patients with impaired renal function (eGFR), specifically those with low estimated Glomerular Filtration Rate (eGFR)?

Aripiprazole Safety in Patients with Low eGFR

Aripiprazole does not require dose adjustment in patients with impaired renal function, regardless of eGFR level, as it has minimal renal clearance and its pharmacokinetics are not significantly altered in renal impairment. 1

Evidence-Based Assessment

The FDA drug label for aripiprazole explicitly states that "no dosage adjustment for aripiprazole is required on the basis of a patient's renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 mL/minute)" 1. This recommendation is based on pharmacokinetic studies that have demonstrated the safety of aripiprazole across various levels of renal function.

Pharmacokinetic Considerations

Research supports the FDA labeling, with studies showing:

• Aripiprazole has negligible renal clearance (only 0.04 mL/h/kg in patients with normal renal function) 2
• A single-dose study comparing patients with severe renal impairment (creatinine clearance <30 mL/min) to those with normal renal function found no meaningful differences in aripiprazole pharmacokinetics that would necessitate dose adjustments 2
• While renal impairment resulted in numerically higher maximum plasma concentrations (approximately 40%), the overall drug exposure was actually slightly lower (19%) in renally impaired subjects compared to those with normal renal function 2

Clinical Implications

When prescribing aripiprazole to patients with low eGFR, consider the following:

1. No dose adjustment required: Unlike many other medications that require dose adjustments in renal impairment, aripiprazole can be dosed normally regardless of eGFR level 1

2. Monitoring considerations: While dose adjustment isn't necessary, standard monitoring for efficacy and side effects should continue as with any patient

3. Medication interactions: Be aware of potential interactions with other medications commonly used in patients with renal impairment, particularly those that might affect CYP2D6 metabolism 1

4. CYP2D6 poor metabolizers: While renal function doesn't require dose adjustment, genetic variations in CYP2D6 metabolism do warrant dosage adjustments due to potentially high aripiprazole concentrations 1

Comparison to Other Psychotropic Medications

Aripiprazole's lack of need for renal dose adjustment contrasts with many other medications used in patients with renal impairment:

• Unlike metformin, which requires dose reduction at eGFR <45 mL/min/1.73m² and avoidance at eGFR <30 mL/min/1.73m² 3
• Unlike some sulfonylureas that are mainly renally excreted and should be avoided in renal impairment 3
• Unlike many antimicrobials that require significant dose adjustments based on renal function 3

Conclusion

Based on the FDA drug label and supporting research evidence, aripiprazole can be safely used in patients with low eGFR without dose adjustment. This makes it a convenient option for patients with renal impairment who require antipsychotic medication, as it eliminates the need for complex dosing calculations or frequent dose adjustments based on changing renal function.