Metoclopramide (Reglan)

• 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

• Generic Name: Metoclopramide
• Brand Names: Reglan, Metozolv ODT, generics

Dopamine (D2) receptor antagonist; prokinetic and antiemetic

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

• 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

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):

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

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)

• 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)

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

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

• 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