What is the approach for Metoclopramide (metoclopramide) reversal?

Metoclopramide Reversal

Metoclopramide-induced extrapyramidal symptoms should be treated immediately with 50 mg diphenhydramine (Benadryl) intramuscularly, or 1-2 mg benztropine mesylate (Cogentin) intramuscularly to reverse the reaction. 1

Understanding Metoclopramide Toxicity

Metoclopramide is a dopamine receptor antagonist commonly used for gastrointestinal motility disorders and as an antiemetic. However, it can cause several extrapyramidal side effects that may require prompt reversal:

1. Acute Dystonic Reactions - Occur in approximately 1 in 500 patients, usually within the first 24-48 hours of treatment. More common in:

   • Pediatric patients
   • Adults under 30 years of age
   • Higher doses (especially with cancer chemotherapy)
   • Symptoms include involuntary movements, facial grimacing, torticollis, oculogyric crisis, tongue protrusion, trismus, and tetanus-like dystonic reactions 1

2. Akathisia - Restlessness and inability to remain still, can occur after even a single dose 2

3. Parkinsonian-like Symptoms - Including bradykinesia, tremor, cogwheel rigidity, or mask-like facies, typically within first 6 months of treatment 1

4. Tardive Dyskinesia - Risk increases with duration of treatment and total cumulative dose 1

5. Neuroleptic Malignant Syndrome (NMS) - Rare but potentially fatal 1

Reversal Protocol

For Acute Dystonic Reactions (First-Line Treatment)

• Administer 50 mg diphenhydramine (Benadryl) intramuscularly 1
• Alternative: 1-2 mg benztropine mesylate (Cogentin) intramuscularly 1

For Parkinsonian-like Symptoms

• Anticholinergic or antiparkinson drugs are helpful in controlling these reactions 1
• Discontinue metoclopramide - symptoms generally subside within 2-3 months 1

For Neuroleptic Malignant Syndrome

1. Immediately discontinue metoclopramide and other non-essential drugs
2. Provide intensive symptomatic treatment and medical monitoring
3. Treat any concomitant serious medical problems
4. Consider bromocriptine and dantrolene sodium (though effectiveness not fully established) 1

For Tardive Dyskinesia

• Discontinue metoclopramide immediately when signs or symptoms appear
• No known effective treatment for established cases
• May partially remit within several weeks to months after withdrawal 1

Special Considerations

Overdose Management

• Symptoms include drowsiness, disorientation, and extrapyramidal reactions
• Anticholinergic drugs, antiparkinson drugs, or antihistamines with anticholinergic properties are helpful
• Symptoms are typically self-limiting and usually disappear within 24 hours
• Hemodialysis removes relatively little metoclopramide 1

High-Risk Populations

• Children have higher risk of extrapyramidal reactions (15% at doses ≥2 mg/kg) 3
• Young adults have increased disposition to acute extrapyramidal reactions 3
• Elderly patients may have increased risk of tardive dyskinesia 1

Prevention Strategies

• Limit metoclopramide treatment to 12 weeks due to risk of tardive dyskinesia 4
• Monitor closely for extrapyramidal symptoms
• Consider discontinuation if symptoms persist despite 3 days of therapy 4
• For children receiving chemotherapy, consider prophylactic diphenhydramine to reduce incidence of extrapyramidal reactions 3

Clinical Pearls

• Extrapyramidal symptoms can occur after a single dose of metoclopramide 2
• Prompt recognition and treatment of these symptoms is crucial to prevent distress
• The oral preparations are recommended for only 4-12 weeks of therapy
• Use of parenteral metoclopramide should be limited to 1-2 days 5

Remember that metoclopramide-induced movement disorders can be very distressing for patients, and prompt recognition and treatment are essential for patient comfort and safety.