Is there an antidote for metoclopramide (metomadine)?

Reversal of Metoclopramide (Metomadine) Effects

Anticholinergic or antiparkinson drugs are the most effective agents for reversing metoclopramide-induced extrapyramidal reactions, while supportive care is sufficient for most overdoses as symptoms are typically self-limiting within 24 hours. 1

Mechanism of Metoclopramide and Its Adverse Effects

Metoclopramide is a dopamine receptor antagonist that works by:

• Blocking dopamine receptors in the central nervous system
• Augmenting acetylcholine release in the gastrointestinal tract
• Coordinating gastric-pyloric-small intestinal motor function 2

The most concerning adverse effects requiring reversal are:

• Extrapyramidal reactions (dystonia, akathisia)
• Drowsiness and sedation
• In severe overdose: disorientation and potentially methemoglobinemia (particularly in neonates) 1

Reversal Strategies for Metoclopramide Effects

For Extrapyramidal Reactions

• First-line treatment: Anticholinergic medications
  • Diphenhydramine (Benadryl) 25-50 mg IV/IM
  • Benztropine (Cogentin) 1-2 mg IV/IM/PO
• Alternative options: Antiparkinson drugs
  • Benztropine 1-2 mg IV/IM/PO
  • Trihexyphenidyl 2-5 mg PO 1

For Overdose Management

1. Supportive care is the mainstay of treatment as symptoms are self-limiting and usually resolve within 24 hours
2. Monitor for:
   • Respiratory depression
   • Cardiovascular effects
   • Neurological status
3. Avoid hemodialysis or peritoneal dialysis as they remove relatively little metoclopramide 1

For Methemoglobinemia (Rare, Primarily in Neonates)

• Methylene blue 1-2 mg/kg IV administered slowly
• Caution: Methylene blue may cause hemolytic anemia in patients with G6PD deficiency 1

Important Clinical Considerations

• Most metoclopramide adverse effects are mild, transient, and reversible upon discontinuation 2, 3
• Extrapyramidal symptoms occur more frequently with:
  • Higher doses (>2 mg/kg in children)
  • Prolonged use (beyond 12 weeks)
  • Younger patients (children and young adults) 4
• The FDA no longer recommends metoclopramide use beyond 12 weeks due to risk of tardive dyskinesia 5

Prevention of Adverse Effects

• Limit metoclopramide use to short durations when possible
• Consider prophylactic diphenhydramine when administering higher doses of metoclopramide, particularly in younger patients 4
• Monitor closely for early signs of extrapyramidal symptoms
• Use the lowest effective dose, especially in elderly patients and children 3

Remember that while reversal agents are effective for acute extrapyramidal reactions, the best approach is prevention through appropriate dosing and duration of therapy.