What is the recommended dose adjustment for metoclopramide (Metoclopramide) in a patient with Chronic Kidney Disease stage 5 (CKD 5)?

Metoclopramide Dosing in CKD Stage 5

For patients with CKD stage 5 (creatinine clearance <40 mL/min), metoclopramide therapy should be initiated at approximately 50% of the standard recommended dosage, with subsequent titration based on clinical efficacy and safety. 1

Dose Adjustment Rationale

• Metoclopramide is excreted principally through the kidneys, making dose reduction essential in severe renal impairment to prevent drug accumulation and toxicity 1
• The FDA label specifically states that when creatinine clearance falls below 40 mL/min, therapy should begin at approximately one-half the recommended dosage 1
• CKD stage 5 represents a GFR <15 mL/min, which falls well below this 40 mL/min threshold requiring dose adjustment 1

Standard Dosing vs. CKD Stage 5 Dosing

• Standard adult dose for diabetic gastroparesis: 10 mg orally four times daily (30 minutes before meals and at bedtime) 1
• CKD stage 5 adjusted dose: Start at 5 mg orally four times daily, or 10 mg twice daily 1
• The dosage may be increased or decreased based on clinical efficacy and safety considerations after initiation 1

Important Safety Considerations

• Extrapyramidal reactions are a significant risk with metoclopramide and may be more pronounced in patients with renal impairment due to drug accumulation 1
• The elimination half-life of metoclopramide in normal renal function is 5-6 hours, but this is significantly prolonged in renal impairment 1
• Renal impairment correlates with reduced plasma clearance, renal clearance, and non-renal clearance, with increased elimination half-life 1
• Drug accumulation occurs with repeated dosing when clearance is impaired 2, 3

Monitoring Requirements

• Close monitoring for adverse effects is essential, particularly sedation and extrapyramidal symptoms (dystonia, akathisia, parkinsonism) 1
• If acute dystonic reactions occur, administer 50 mg diphenhydramine intramuscularly 1
• Reassess the risk-benefit ratio regularly, as metoclopramide carries a black box warning for tardive dyskinesia with prolonged use 1

Dialysis Considerations

• Metoclopramide undergoes minimal hepatic metabolism and is primarily renally eliminated 1
• While the FDA label mentions dialysis in the overdosage section, specific supplemental dosing recommendations for hemodialysis or peritoneal dialysis are not provided 1
• Dialysis techniques may remove drugs from the body, potentially necessitating additional dose adjustments 2