What is the recommended dose of metoclopramide (Reglan) for a patient with severe impaired renal function (creatinine clearance of 21)?

Metoclopramide Dosing in Patients with Renal Impairment (CrCl 21 mL/min)

For a patient with creatinine clearance of 21 mL/min, metoclopramide should be initiated at approximately one-half the recommended dosage (i.e., 5 mg instead of 10 mg per dose). 1

Pharmacokinetics in Renal Impairment

• Metoclopramide is primarily excreted through the kidneys, with renal impairment significantly affecting its clearance 1, 2
• Studies show that reduced creatinine clearance correlates with reduced plasma clearance, renal clearance, and non-renal clearance of metoclopramide 1
• The elimination half-life increases in patients with renal impairment, potentially leading to drug accumulation with standard dosing 2
• Although renal clearance accounts for ≤21% of total plasma clearance, non-renal clearance is also reduced in patients with renal impairment 2

Specific Dosing Recommendations

• The FDA label specifically states: "Since metoclopramide is excreted principally through the kidneys, in those patients whose creatinine clearance is below 40 mL/min, therapy should be initiated at approximately one-half the recommended dosage" 1
• For a standard 10 mg dose, this would mean starting with 5 mg per dose 1
• Dosage may be increased or decreased based on clinical efficacy and safety considerations 1
• The drug's kinetics remain linear in renal impairment, but clearance is reduced, necessitating dose adjustment 1

Monitoring Recommendations

• Patients with renal impairment should be observed carefully for adverse reactions 1
• If adverse effects occur, further dose reduction or discontinuation of the drug may be necessary 1
• Common side effects include sedation and, less commonly, extrapyramidal reactions 1
• More severe side effects (behavioral changes, delirium, hallucinations) have been associated with high plasma drug concentrations, particularly in patients with renal insufficiency 3

Hemodialysis Considerations

• Hemodialysis contributes minimally to metoclopramide clearance 1, 2
• Compensatory dosage increases are generally unnecessary for patients on hemodialysis 2
• Hemodialysis is unlikely to be effective in cases of metoclopramide overdose 2

Clinical Implications

• The comparatively small plasma clearances in patients with renal impairment imply that maintenance doses should be reduced to avoid drug accumulation 2
• Metoclopramide at normal doses (<0.2 mg/kg) does not appear to antagonize the renal effects of low-dose dopamine infusions in critically ill patients 4
• Elderly patients often have decreased renal function and may require additional dose considerations beyond those based solely on creatinine clearance 3

Practical Approach

• Start with 5 mg per dose (half the standard dose) 1
• Monitor for efficacy and adverse effects 1
• Adjust dosage based on clinical response and tolerability 1
• Be particularly vigilant for extrapyramidal symptoms and CNS effects, which may be more common with drug accumulation 3, 1