Aripiprazole Dosing in Renal Impairment
No dosage adjustment for aripiprazole is required in patients with renal impairment, regardless of severity (mild to severe renal impairment, glomerular filtration rate between 15 and 90 mL/minute). 1
Pharmacokinetic Basis
- Aripiprazole does not require dose adjustment in renal impairment because its renal clearance is negligible (only 0.04 mL/h/kg in patients with normal renal function) 2
- Studies have shown no meaningful differences in aripiprazole pharmacokinetics between subjects with normal renal function and those with severe renal impairment (creatinine clearance <30 mL/min) 2
- The fraction of unbound aripiprazole remains comparable between patients with normal renal function and those with renal impairment, unlike many other medications that may have altered protein binding in kidney disease 2
Clinical Evidence
- FDA labeling specifically states that no dosage adjustment is required based on a patient's renal function, even in severe renal impairment 1
- This recommendation is supported by pharmacokinetic studies demonstrating that renal elimination is not a significant pathway for aripiprazole clearance 2
- Unlike many other psychotropic medications that require careful dose adjustments in renal dysfunction, aripiprazole maintains a consistent pharmacokinetic profile across all levels of renal function 1, 2
Contrast with Other Medications
- This is notably different from many other medications that require significant dosage adjustments in renal impairment 3, 4
- For example, many calcium channel α-δ ligands like gabapentin and pregabalin require dose reductions in impaired renal function 5
- Similarly, medications like chlorpromazine require cautious use and potential dose adjustments in patients with renal impairment 5
Clinical Considerations
- While no dose adjustment is needed, monitoring for adverse effects is still recommended, particularly in elderly patients who may have age-related decreases in renal function 1
- Common adverse effects to monitor include gastrointestinal effects, headache, and potential psychiatric symptoms 5
- Unlike medications that are primarily eliminated through the kidneys, aripiprazole is primarily metabolized by hepatic enzymes (CYP2D6 and CYP3A4) 1, 2
Special Populations
- In patients who are CYP2D6 poor metabolizers, dosage adjustment is recommended due to high aripiprazole concentrations, regardless of renal function 1
- No additional dosage adjustment is required based on a patient's sex, race, or smoking status 1
- For elderly patients, while no specific renal-based adjustment is needed, caution is generally advised due to increased sensitivity to adverse effects 1
Practical Application
- When prescribing aripiprazole to patients with renal impairment, standard dosing protocols can be followed 1, 2
- This simplifies medication management in patients with comorbid psychiatric conditions and kidney disease 2
- Focus monitoring on potential adverse effects rather than adjusting the dose based on renal function 1