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Bedside Snapshot
  • Core Use: D2 antagonist with both antiemetic and prokinetic effects (enhances gastric emptying and small bowel transit)
  • Typical ED Dose: 10 mg IV for nausea/vomiting, gastroparesis flares, and as a migraine adjunct (often with diphenhydramine to reduce dystonia/akathisia)
  • Onset/Duration: IV onset within 1–3 minutes; oral onset 30–60 minutes; elimination half-life ~5–6 hours in normal renal function
  • Key Dangers: Extrapyramidal symptoms (EPS), acute dystonic reactions, akathisia, sedation, diarrhea, and with chronic use tardive dyskinesia (boxed warning)
  • Special Notes: Can prolong QT modestly and lower seizure threshold; useful in gastroparesis and for facilitating gastric emptying before procedures, but avoid if mechanical obstruction is suspected
Brand & Generic Names
  • Generic Name: Metoclopramide
  • Brand Names: Reglan, Metozolv ODT, generics
Medication Class

Dopamine (D2) receptor antagonist; prokinetic and antiemetic

Pharmacology

Mechanism of Action:

  • Central D2 receptor antagonism in the chemoreceptor trigger zone (CTZ) provides antiemetic effect
  • Peripheral D2 antagonism in the GI tract increases acetylcholine release and enhances gastric motility, increasing lower esophageal sphincter tone and accelerating gastric emptying
  • At higher doses, has some 5-HT3 antagonist and 5-HT4 agonist activity, further contributing to antiemetic and prokinetic effects
  • D2 blockade in the basal ganglia is responsible for EPS, dystonia, and tardive dyskinesia risk with repeated or high-dose use

Pharmacokinetics:

  • Absorption: Oral bioavailability ~80%; onset of antiemetic effect within 30–60 minutes PO; IV onset within 1–3 minutes
  • Distribution: Crosses blood–brain barrier; volume of distribution ~3–4 L/kg
  • Metabolism: Hepatic (CYP2D6 and others) with significant first-pass effect; some renally excreted unchanged
  • Elimination: Primarily renal; elimination half-life ~5–6 hours in normal renal function, prolonged in kidney disease
  • Special Considerations: Dose reductions or prolonged dosing intervals are recommended in renal impairment and in older adults
Indications
  • Symptomatic treatment of nausea and vomiting, particularly with suspected gastroparesis or functional dyspepsia
  • Adjunct in migraine treatment (e.g., 10 mg IV plus diphenhydramine, often with fluids and NSAIDs)
  • Short-term treatment of diabetic gastroparesis or gastric stasis in ICU patients (via IV or enteral dosing)
  • Prevention/treatment of post-op nausea and vomiting in some protocols when other agents are inadequate or contraindicated
Dosing & Administration

Available Forms:

  • Injection: 5 mg/mL in vials (commonly 2 mL = 10 mg)
  • Tablets: 5 mg, 10 mg
  • Orally disintegrating tablets (ODT): 5 mg, 10 mg
  • Oral solution: typically 5 mg/5 mL (verify concentration)

Dosing Guidelines (Adult):

Indication / Route Typical Dose Frequency Notes
Nausea/vomiting (IV/IM) 10 mg IV/IM Once; may repeat q6h PRN Give IV over 1–2 min; monitor for akathisia/EPS
Migraine adjunct (IV) 10–20 mg IV Once Commonly 10 mg with diphenhydramine; higher doses per protocol
Diabetic gastroparesis (PO) 10 mg PO 30 minutes before meals and at bedtime Short-term use (e.g., up to 12 weeks) due to tardive dyskinesia risk
ICU gastric motility (NG/OG or IV) 5–10 mg Every 6–8 hours Tailor to renal function and side effects
Renal impairment (CrCl <40 mL/min) Reduce dose by ~50% Extend interval (e.g., q8–12h) Higher EPS risk when drug accumulates
Elderly 5 mg Every 6–8 hours PRN Increased sensitivity to EPS and sedation
Maximum daily dose (usual adult) 40–60 mg/day Divided doses Avoid high doses or prolonged use when possible
Contraindications

Contraindications:

  • Known hypersensitivity to metoclopramide or other components of the formulation
  • History of tardive dyskinesia or EPS with dopamine antagonists
  • Suspected or confirmed GI mechanical obstruction, perforation, or GI hemorrhage (risk of worsening obstruction or perforation)
  • Pheochromocytoma (risk of hypertensive crisis)
  • Use with other drugs that have a high risk of causing EPS or tardive dyskinesia without strong justification

Major Precautions:

  • Use caution in patients with Parkinson disease or other movement disorders; dopamine blockade can significantly worsen symptoms
  • Can cause or worsen EPS (dystonia, akathisia, parkinsonism), especially in younger adults, high doses, or repeated IV dosing
  • May cause QT prolongation and lower seizure threshold; use caution in patients with seizure disorders or baseline QT prolongation
  • Reduce dose and monitor closely in renal impairment and in elderly patients
BOXED WARNING - Tardive Dyskinesia: Risk of tardive dyskinesia increases with total duration and cumulative dose. Avoid treatment longer than 12 weeks when possible. Tardive dyskinesia may be irreversible.
Adverse Effects

Common:

  • Sedation, fatigue, restlessness
  • Diarrhea, abdominal cramping
  • Akathisia (inner restlessness, pacing)
  • Mild headache, dizziness

Serious:

  • Acute dystonic reactions (e.g., oculogyric crisis, torticollis, jaw spasm)
  • Tardive dyskinesia with chronic use (involuntary facial/tongue or limb movements)
  • Neuroleptic malignant syndrome (rare)
  • Severe EPS and parkinsonism, especially in older adults
  • QT prolongation and arrhythmias (rare, but caution with other QT-prolonging drugs)
Drug Interactions
  • Other dopamine antagonists: Increased risk of EPS and tardive dyskinesia (e.g., prochlorperazine, promethazine, antipsychotics)
  • QT-prolonging drugs: Additive QT prolongation risk (e.g., amiodarone, haloperidol, fluoroquinolones)
  • Anticholinergics: May antagonize prokinetic effects of metoclopramide
  • Levodopa/Carbidopa: Metoclopramide may worsen Parkinson symptoms and reduce levodopa efficacy
  • CNS depressants: Additive sedation (e.g., benzodiazepines, opioids, alcohol)
Special Populations

Elderly Patients:

  • Start with lowest dose (5 mg) and monitor closely for EPS, sedation, and parkinsonism
  • Higher risk of tardive dyskinesia with even short-term use

Renal Impairment:

  • CrCl <40 mL/min: Reduce dose by approximately 50% and extend dosing interval
  • Monitor for drug accumulation and increased risk of EPS

Hepatic Impairment:

  • Use with caution; dose adjustment may be necessary
  • Monitor for increased sedation and CNS effects

Pregnancy:

  • Category B: No evidence of risk in human studies
  • Often used for hyperemesis gravidarum when benefits outweigh risks

Lactation:

  • Excreted in breast milk; use with caution
  • May increase milk production via prolactin elevation
  • Monitor infant for sedation or GI effects
Monitoring

Clinical Monitoring:

  • Clinical response: reduction of nausea/vomiting, improvement in gastric emptying symptoms, or migraine relief
  • Observe for akathisia or dystonic reactions within hours of IV dosing; treat with diphenhydramine or benztropine if present
  • Monitor mental status and sedation, especially when combined with opioids or other CNS depressants

Laboratory Monitoring:

  • Consider ECG monitoring in patients at risk for QT prolongation or on multiple QT-prolonging drugs
  • In longer use (ward/clinic), monitor for signs of tardive dyskinesia or parkinsonism and discontinue if they appear
Clinical Pearls
Migraine Cocktail: In migraine cocktails, metoclopramide often works best when combined with diphenhydramine both for additive benefit and to reduce akathisia/dystonia.
Gastroparesis Advantage: In suspected gastroparesis, metoclopramide is often more helpful than pure 5-HT3 antagonists because of its prokinetic effect.
EPS Risk with Repeated Dosing: Avoid repeated high-dose IV dosing in the same visit when possible; the risk of EPS climbs quickly with cumulative exposure.
Class Reaction: If a patient has a documented dystonic reaction to metoclopramide, treat as a class reaction and avoid other D2-blocking antiemetics (e.g., prochlorperazine) when possible.
Dystonia Treatment: Acute dystonic reactions respond rapidly to diphenhydramine 25–50 mg IV or benztropine 1–2 mg IV/IM. Keep rescue agents readily available when administering metoclopramide.
References
  • 1. Lexicomp. (2024). Metoclopramide: Drug information. Wolters Kluwer.
  • 2. American Gastroenterological Association. (2013). Technical review on the diagnosis and treatment of gastroparesis. Gastroenterology, 145(5), 1240–1271. https://doi.org/10.1053/j.gastro.2013.08.071
  • 3. American Headache Society. (2016). Management of adults with acute migraine in the emergency department. Headache, 56(6), 911–940. https://doi.org/10.1111/head.12835
  • 4. U.S. Food and Drug Administration. (2009). FDA requires boxed warning and risk mitigation strategy for metoclopramide-containing drugs [Press release]. https://www.fda.gov/news-events/press-announcements/fda-requires-boxed-warning-and-risk-mitigation-strategy-metoclopramide-containing-drugs
  • 5. Rao, A. S., & Camilleri, M. (2010). Review article: Metoclopramide and tardive dyskinesia. Alimentary Pharmacology & Therapeutics, 31(1), 11–19. https://doi.org/10.1111/j.1365-2036.2009.04189.x
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