Reglan - Drug Monograph

Introduction

Reglan (metoclopramide) is a dopamine receptor antagonist and prokinetic agent primarily used to manage gastrointestinal disorders. First approved by the FDA in 1979, it remains an important therapeutic option despite significant safety considerations, particularly regarding neurological side effects.

Mechanism of Action

Metoclopramide exerts its effects through multiple mechanisms:

• Dopamine D2 receptor antagonism in the chemoreceptor trigger zone, providing antiemetic effects
• 5-HT4 receptor agonism enhancing acetylcholine release in the myenteric plexus
• Cholinergic effects by sensitizing tissues to acetylcholine
• Gastric prokinetic effects through increased lower esophageal sphincter tone, improved gastric emptying, and enhanced duodenal and jejunal peristalsis

Indications

• Diabetic gastroparesis (symptomatic relief)
• Gastroesophageal reflux disease
• Prevention of postoperative nausea and vomiting
• Facilitating small bowel intubation
• Radiological evaluation of GI tract

• Chemotherapy-induced nausea and vomiting
• Migraine-associated nausea
• Refractory hiccups
• Facilitate enteral feeding tolerance

Dosage and Administration

• Diabetic gastroparesis: 10 mg PO 30 minutes before meals and at bedtime
• GERD: 10-15 mg PO up to QID before meals and at bedtime
• Postoperative N/V: 10-20 mg IM at end of procedure

• Renal impairment: CrCl <40 mL/min: reduce dose by 50%
• Hepatic impairment: Use with caution, consider dose reduction
• Elderly: Lower initial doses recommended due to increased sensitivity
• Pediatrics: Limited use due to risk of tardive dyskinesia

Pharmacokinetics

• Absorption: Rapid and complete oral absorption (bioavailability 80-95%)
• Distribution: Vd ~3.5 L/kg; crosses blood-brain barrier and placenta
• Metabolism: Hepatic via oxidation, glucuronidation, and sulfation
• Elimination: Half-life 4-6 hours; renal excretion (85% of dose)
• 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 (may lower seizure threshold)

Warnings and Precautions

• Neuroleptic malignant syndrome (rare but potentially fatal)
• Depression and suicide ideation
• Parkinsonian symptoms
• Hyperprolactinemia and associated effects
• Cardiac effects including bradycardia and heart block
• Use in elderly and diabetic patients with autonomic neuropathy

Drug Interactions

• CNS depressants: Enhanced sedation (alcohol, opioids, benzodiazepines)
• Anticholinergics: Antagonizes prokinetic effects
• Dopaminergic agents: Reduced efficacy (levodopa, bromocriptine)
• CYP2D6 inhibitors: Increased metoclopramide levels (fluoxetine, paroxetine)
• Digoxin: Reduced absorption
• Succinylcholine: Enhanced neuromuscular blockade

Adverse Effects

• Restlessness
• Drowsiness
• Fatigue
• Diarrhea
• Dystonic reactions (especially in young patients)

• Tardive dyskinesia (risk: 1% with >12 weeks use)
• Neuroleptic malignant syndrome
• Depression with suicidal ideation
• Parkinsonian symptoms
• Hyperprolactinemia (galactorrhea, gynecomastia)
• Blood dyscrasias (agranulocytosis)

Monitoring Parameters

• Neurological examination for EPS and TD (baseline and regularly during treatment)
• Mental status changes
• Signs of NMS (fever, rigidity, autonomic instability)
• Prolactin levels if symptomatic
• Renal and hepatic function
• Therapeutic response and need for continued therapy

Patient Education

• Take 30 minutes before meals and at bedtime as directed
• Do not exceed prescribed dose or duration
• Report immediately: involuntary movements, muscle stiffness, fever, or mental changes
• Avoid alcohol and other CNS depressants
• Be cautious when driving or operating machinery due to drowsiness
• Understand risk of tardive dyskinesia with prolonged use
• Do not stop abruptly without medical supervision

References

1. FDA Prescribing Information: Reglan (metoclopramide) 2. Miller LJ. Metoclopramide: a review of its clinical use. Gastroenterol Clin North Am. 1989;18(2):677-688. 3. Bateman DN. Clinical pharmacokinetics of metoclopramide. Clin Pharmacokinet. 1983;8(6):523-529. 4. Kenney C, et al. Metoclopramide, an increasingly recognized cause of tardive dyskinesia. J Clin Pharmacol. 2008;48(3):379-384. 5. Pasricha PJ, et al. ACG Clinical Guideline: Gastroparesis. Am J Gastroenterol. 2022;117(8):1197-1220. 6. USP DI: Metoclopramide. 2023 Drug Points® System