What is the appropriate treatment for an adult who has overdosed on metoclopramide (Reglan)?

Management of Metoclopramide (Reglan) Overdose

For metoclopramide overdose, immediately administer anticholinergic agents (diphenhydramine or benztropine) or antiparkinson drugs to control extrapyramidal reactions, which are the primary manifestation of toxicity, and provide supportive care as symptoms are self-limiting and typically resolve within 24 hours. 1

Primary Clinical Manifestations

Metoclopramide overdose presents with three cardinal features:

• Drowsiness and disorientation are common initial symptoms 1
• Extrapyramidal reactions (dystonia, neck rigidity, upward eye deviation) are the most concerning manifestations and can occur within 2-6 hours of ingestion 1, 2
• Symptoms are self-limiting and usually disappear within 24 hours without intervention 1

Immediate Treatment Protocol

First-Line Pharmacologic Management

Administer anticholinergic or antiparkinson medications immediately upon recognition of extrapyramidal symptoms:

• Diphenhydramine (antihistamine with anticholinergic properties) is the most accessible first-line agent 1
• Benztropine or other antiparkinson drugs are equally effective alternatives 1
• Biperiden 5 mg IM can be used, though case reports show variable response requiring repeat dosing at 12-hour intervals 2
• Diazepam has demonstrated efficacy in resolving symptoms within 6 hours in documented cases of severe reactions 3

Supportive Care Measures

• Monitor for 24 hours as symptoms are self-limiting 1
• Provide reassurance to patients and families, as dystonic reactions can be frightening but are reversible 2
• Avoid gastric decontamination methods as they are unlikely to be beneficial and metoclopramide is rapidly absorbed 1

Special Considerations and High-Risk Scenarios

Dialysis is NOT Effective

• Hemodialysis removes minimal metoclopramide due to extensive tissue distribution 1
• Continuous ambulatory peritoneal dialysis is similarly ineffective 1
• Dosage adjustment for dialysis losses is unnecessary and dialysis should not be pursued as a treatment strategy 1

Pediatric Overdose Complications

Infants and children face unique risks with metoclopramide overdose:

• Seizures, extrapyramidal reactions, and lethargy are the predominant manifestations in pediatric populations 1
• Methemoglobinemia can occur in premature and full-term neonates receiving 1-4 mg/kg/day for 1-3 days 1
• Methylene blue reverses methemoglobinemia but is contraindicated in G6PD deficiency due to risk of fatal hemolytic anemia 1
• Extrapyramidal effects occur at doses as low as 3 mg/kg in infants, as documented in a case of a 6-month-old receiving 24 mg over 9 hours 4

Drug Interaction Complications

Patients on serotonergic medications face amplified risks:

• Serotonin syndrome with severe extrapyramidal reactions can occur when metoclopramide is combined with SSRIs (sertraline) or SNRIs (venlafaxine), even with single conventional doses 3
• Symptoms include agitation, dysarthria, diaphoresis, movement disorders, confusion, fever, tachycardia, and hypertension 3
• Treatment requires benzodiazepines (diazepam) with potential need for repeated dosing over 16 hours 3

Risk Stratification by Patient Population

Highest Risk Groups for Severe Reactions

• Patients under 30 years have increased risk of acute dystonic reactions 5
• Elderly patients, females, and diabetics are at higher risk for tardive dyskinesia with chronic exposure 5
• Patients with Parkinson's disease may experience symptom exacerbation 5
• Patients with depression history risk severe depression and suicidal ideation 5

Critical Pitfalls to Avoid

• Do NOT misdiagnose dystonic reactions as seizures or other neurologic emergencies, leading to inappropriate workup and delayed treatment 2
• Do NOT assume prolonged treatment is needed beyond symptomatic management, as reactions resolve spontaneously 1
• Do NOT use methylene blue in patients with unknown G6PD status without considering the risk of fatal hemolytic anemia 1
• Do NOT overlook concurrent serotonergic medications that may precipitate serotonin syndrome requiring more aggressive benzodiazepine therapy 3

Disposition and Monitoring

• Observe for minimum 24 hours to ensure complete symptom resolution 1
• Monitor for recurrence if repeat anticholinergic dosing is required 2
• Psychiatric evaluation should be obtained for intentional overdoses 6
• Patient education regarding proper dosing is essential to prevent recurrence, particularly given the maximum recommended dose of 30 mg/day and duration limited to 5 days 7