Introduction
Metoclopramide is a dopamine receptor antagonist and prokinetic agent that has been widely used in clinical practice since the 1960s. This medication primarily affects gastrointestinal motility and is classified as an antiemetic. It remains an important therapeutic option despite the availability of newer agents, particularly for specific gastrointestinal disorders and chemotherapy-induced nausea.
Mechanism of Action
Metoclopramide exerts its effects through multiple mechanisms:
- Dopamine D₂ receptor antagonism: Blocks dopamine receptors in the chemoreceptor trigger zone (CTZ), reducing nausea and vomiting signals
- Cholinergic effects: Stimulates acetylcholine release in the myenteric plexus, enhancing gastric emptying and intestinal transit
- Serotonin receptor effects: Weak 5-HT₃ receptor antagonism and 5-HT₄ receptor agonism contribute to its prokinetic and antiemetic properties
Indications
FDA-approved indications:- Diabetic gastroparesis (symptomatic relief)
- Prevention of chemotherapy-induced nausea and vomiting
- Prevention of postoperative nausea and vomiting
- Gastroesophageal reflux disease (GERD) in patients who have failed conventional therapy
- Non-ulcer dyspepsia
- Migraine-associated nausea
- Facilitating small bowel intubation
- Radiographic contrast studies
- Adjunct in pain control for renal colic
Dosage and Administration
Adults:- Diabetic gastroparesis: 10 mg PO 30 minutes before meals and at bedtime (max 40 mg/day)
- GERD: 10-15 mg PO up to 4 times daily
- Chemotherapy-induced nausea: 1-2 mg/kg IV 30 minutes before chemotherapy, then q2h for two doses, then q3h for three doses
- Postoperative nausea: 10 mg IM at end of surgery
- Renal impairment: Reduce dose by 50% for CrCl <40 mL/min
- Hepatic impairment: Use with caution; consider dose reduction
- Elderly: Start with lower doses due to increased sensitivity
- Pediatrics: Limited use; 0.1-0.2 mg/kg/dose (max 10 mg)
Pharmacokinetics
- Absorption: Rapid and complete oral absorption (bioavailability 80-85%)
- Distribution: Widely distributed; crosses blood-brain barrier and placenta
- Protein binding: Approximately 30%
- Metabolism: Hepatic via oxidation, glucuronidation, and sulfation
- Elimination: Half-life 4-6 hours; primarily renal excretion (85%)
- Onset of action: Oral: 30-60 minutes; IV: 1-3 minutes
Contraindications
- Known hypersensitivity to metoclopramide
- Gastrointestinal obstruction, perforation, or hemorrhage
- Pheochromocytoma
- History of tardive dyskinesia
- Concomitant use with drugs likely to cause extrapyramidal symptoms
- Epilepsy (relative contraindication)
Warnings and Precautions
Black Box Warning: Tardive dyskinesia (risk increases with duration of treatment and total cumulative dose)- Extrapyramidal symptoms: Dystonia, akathisia, parkinsonism (more common in children/young adults)
- Neuroleptic malignant syndrome: Rare but potentially fatal
- Depression: May exacerbate or cause depression
- Cardiac effects: Possible QT prolongation
- Hyperprolactinemia: May cause galactorrhea, gynecomastia, menstrual irregularities
- Suicidality: Monitor for mood changes
Drug Interactions
- CNS depressants: Enhanced sedation with alcohol, opioids, benzodiazepines
- Anticholinergics: May antagonize prokinetic effects
- Dopaminergic agents: Reduced efficacy of levodopa, bromocriptine
- Cytochrome P450 2D6 inhibitors: May increase metoclopramide levels
- Drugs that prolong QT interval: Additive effects (antiarrhythmics, antipsychotics)
- Digoxin: May decrease absorption
Adverse Effects
Common (≥1%):- Drowsiness, fatigue, restlessness
- Diarrhea, nausea
- Extrapyramidal symptoms (especially acute dystonic reactions)
- Tardive dyskinesia (often irreversible)
- Neuroleptic malignant syndrome
- Depression, suicidal ideation
- Cardiac arrhythmias, QT prolongation
- Hyperprolactinemia-related effects
- Blood dyscrasias (agranulocytosis)
Monitoring Parameters
- Efficacy: Symptom improvement in nausea, vomiting, gastric emptying
- Neurological: Regular assessment for extrapyramidal symptoms, especially with prolonged use
- Mental status: Mood changes, depression, suicidal ideation
- Prolactin levels: If symptoms of hyperprolactinemia occur
- Renal function: In patients with renal impairment
- ECG: In patients at risk for QT prolongation
Patient Education
- Take 30 minutes before meals for gastroparesis
- Avoid alcohol and other CNS depressants
- Report immediately: Muscle spasms, involuntary movements, mood changes
- Be cautious when driving or operating machinery due to drowsiness
- Do not exceed prescribed dose or duration
- Understand risk of tardive dyskinesia with long-term use
- Seek medical attention if symptoms worsen or new symptoms develop
References
1. FDA Prescribing Information: Reglan (metoclopramide) tablets 2. American Gastroenterological Association Technical Review on Gastroparesis. Gastroenterology 2013 3. ASCO Guidelines for Antiemetics in Oncology: J Clin Oncol 2020 4. Bateman DN. Clinical pharmacology of metoclopramide. Br J Clin Pharmacol 2021 5. Pasricha PJ, et al. Diabetic Gastroparesis: Trends and Technologies. Gastroenterology 2022 6. Miller LG, et al. Tardive Dyskinesia: A Review. Mov Disord Clin Pract 2023 7. UpToDate Drug Information: Metoclopramide (accessed 2023) 8. Micromedex® Healthcare Series: Metoclopramide monograph
This information is for educational purposes only and does not constitute medical advice. Always consult with a healthcare professional for personalized medical recommendations.