Metoclopramide and Ondansetron: Nephrotoxicity Assessment
Neither metoclopramide nor ondansetron are directly nephrotoxic medications, but ondansetron may enhance nephrotoxicity when combined with certain drugs like cisplatin through inhibition of multidrug and toxin extrusion proteins (MATEs).
Metoclopramide and Nephrotoxicity
Metoclopramide has not been associated with direct nephrotoxicity based on available evidence. The FDA drug label for metoclopramide does not list nephrotoxicity as a known adverse effect 1. While metoclopramide is excreted in human milk and dose adjustments are recommended for elderly patients with impaired renal function, this is due to altered drug clearance rather than kidney injury risk.
Key points regarding metoclopramide:
- No direct nephrotoxic effects reported in clinical guidelines or FDA labeling
- Dose adjustment is recommended in patients with impaired renal function due to altered clearance, not due to nephrotoxicity concerns
- Primary side effects are extrapyramidal symptoms, particularly in elderly and pediatric populations 1
Ondansetron and Nephrotoxicity
Ondansetron itself is not directly nephrotoxic, but research suggests it may enhance nephrotoxicity of certain medications through specific mechanisms:
Inhibition of MATEs: Ondansetron can inhibit multidrug and toxin extrusion proteins (MATEs), which are important for elimination of certain drugs from kidney cells 2.
Cisplatin interaction: When combined with cisplatin (a known nephrotoxic chemotherapeutic agent), ondansetron may enhance cisplatin-induced nephrotoxicity by inhibiting MATEs, leading to increased renal accumulation of cisplatin 2.
Renal clearance: Only about 5% of ondansetron is excreted unchanged in urine, with most elimination occurring through hepatic metabolism 3.
Recent evidence: A 2022 study in critically ill patients found that ondansetron was not associated with increased risk of acute kidney injury compared to other antiemetics like metoclopramide 4.
Clinical Implications and Recommendations
When choosing between these antiemetics:
For general use: Both medications can be used safely in patients with normal renal function without significant concern for nephrotoxicity.
For patients receiving cisplatin: Consider avoiding ondansetron due to its potential to enhance cisplatin-induced nephrotoxicity through MATE inhibition 2.
For patients with renal impairment:
- Metoclopramide: Use with caution and consider dose reduction in severe renal impairment
- Ondansetron: Renal impairment is not expected to significantly influence clearance as renal elimination represents only 5% of overall clearance 3
For patients with uremia-induced nausea/vomiting: Ondansetron appears more effective than metoclopramide in controlling symptoms 5.
For renal colic: Ondansetron was found to be more effective than metoclopramide in preventing and improving vomiting in patients with renal colic 6.
Practical Considerations
Both medications are commonly used as antiemetics in clinical practice, including in guidelines for pregnancy-related nausea and vomiting 7 and for patients receiving PRRT (Peptide Receptor Radionuclide Therapy) 7.
When administering either medication to patients with existing renal impairment, monitor kidney function as a general precaution, especially if combined with other potentially nephrotoxic agents.
In patients receiving multiple medications, consider the overall "nephrotoxic burden" rather than focusing on a single agent 7.
Remember that while these medications themselves have limited direct nephrotoxic potential, the clinical context and medication combinations should always be considered when assessing overall risk to kidney function.